Skip to main content
SpringerLink
Log in

Contribution and Expression of Organic Cation Transporters and Aquaporin Water Channels in Renal Cancer

  • Chapter
  • First Online:
Transportome Malfunction in the Cancer Spectrum

Part of the book series: Reviews of Physiology, Biochemistry and Pharmacology ((REVIEWS,volume 181))

Abstract

The body homeostasis is maintained mainly by the function of the kidneys, which regulate salt and water balance and excretion of metabolism waste products and xenobiotics. This important renal function is determined by the action of many transport systems, which are specifically expressed in the different parts of the nephron, the functional unit of the kidneys. These transport systems are involved, for example, in the reabsorption of sodium, glucose, and other important solutes and peptides from the primary urine. They are also important in the reabsorption of water and thereby production of a concentrated urine. However, several studies have shown the importance of transport systems for different tumor entities. Transport systems, for example, contributed to the proliferation and migration of cancer cells and thereby on tumor progression. They could also serve as drug transporters that could enable drug resistance by outward transport of, for example, chemotherapeutic agents and other drugs. Although many renal transporters have been characterized in detail with respect to the significance for proper kidney function, their role in renal cancer progression is less known. Here, we describe the types of renal cancer and review the studies that analyzed the role of organic cation transporters of the SLC22-family and of the aquaporin water channel family in kidney tumors.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Ambrosetti D, Dufies M, Dadone B, Durand M, Borchiellini D, Amiel J, Pouyssegur J, Rioux-Leclercq N, Pages G, Burel-Vandenbos F, Mazure NM (2018) The two glycolytic markers GLUT1 and MCT1 correlate with tumor grade and survival in clear-cell renal cell carcinoma. PLoS One 13:e0193477

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Amemiya M, Loffing J, Lotscher M, Kaissling B, Alpern RJ, Moe OW (1995) Expression of NHE-3 in the apical membrane of rat renal proximal tubule and thick ascending limb. Kidney Int 48:1206–1215

    Article  CAS  PubMed  Google Scholar 

  • Ancey PB, Contat C, Meylan E (2018) Glucose transporters in cancer - from tumor cells to the tumor microenvironment. FEBS J 285:2926–2943

    Article  CAS  PubMed  Google Scholar 

  • Arnold M, Pandeya N, Byrnes G, Renehan PAG, Stevens GA, Ezzati PM, Ferlay J, Miranda JJ, Romieu I, Dikshit R, Forman D, Soerjomataram I (2015) Global burden of cancer attributable to high body-mass index in 2012: a population-based study. Lancet Oncol 16:36–46

    Article  PubMed  Google Scholar 

  • Bhutia YD, Babu E, Ramachandran S, Ganapathy V (2015) Amino acid transporters in cancer and their relevance to "glutamine addiction": novel targets for the design of a new class of anticancer drugs. Cancer Res 75:1782–1788

    Article  CAS  PubMed  Google Scholar 

  • Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424

    Article  PubMed  Google Scholar 

  • Capitanio U, Montorsi F (2016) Renal cancer. Lancet 387:894–906

    Article  PubMed  Google Scholar 

  • Capitanio U, Terrone C, Antonelli A, Minervini A, Volpe A, Furlan M, Matloob R, Regis F, Fiori C, Porpiglia F, DI Trapani E, Zacchero M, Serni S, Salonia A, Carini M, Simeone C, Montorsi F, Bertini R (2015) Nephron-sparing techniques independently decrease the risk of cardiovascular events relative to radical nephrectomy in patients with a T1a-T1b renal mass and normal preoperative renal function. Eur Urol 67:683–689

    Article  PubMed  Google Scholar 

  • Chen L, Hong C, Chen EC, Yee SW, Xu L, Almof EU, Wen C, Fujii K, Johns SJ, Stryke D, Ferrin TE, Simko J, Chen X, Costello JF, Giacomini KM (2013) Genetic and epigenetic regulation of the organic cation transporter 3, SLC22A3. Pharmacogenomics J 13:110–120

    Article  CAS  PubMed  Google Scholar 

  • Cheng JX, Tretiakova M, Gong C, Mandal S, Krausz T, Taxy JB (2008) Renal medullary carcinoma: rhabdoid features and the absence of INI1 expression as markers of aggressive behavior. Mod Pathol 21:647–652

    Article  CAS  PubMed  Google Scholar 

  • Choueiri TK, Motzer RJ (2017) Systemic therapy for metastatic renal-cell carcinoma. N Engl J Med 376:354–366

    Article  CAS  PubMed  Google Scholar 

  • Ciarimboli G, Ludwig T, Lang D, Pavenstñdt H, Koepsell H, Piechota HJR, Haier J, Jaehde U, Zisowsky J, Schlatter E (2005) Cisplatin nephrotoxicity is critically mediated via the human organic cation transporter 2. Am J Pathol 167:1477–1484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ciarimboli G, Deuster D, Knief A, Sperling M, Holtkamp M, Edemir B, Pavenstadt H, Lanvers-Kaminsky C, Am Zehnhoff-Dinnesen A, Schinkel AH, Koepsell H, Jurgens H, Schlatter E (2010) Organic cation transporter 2 mediates cisplatin-induced Oto- and nephrotoxicity and is a target for protective interventions. Am J Pathol 176:1169–1180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ciarimboli G, Holle SK, Vollenbrocker B, Hagos Y, Reuter S, Burckhardt G, Bierer S, Herrmann E, Pavenstadt H, Rossi R, Kleta R, Schlatter E (2011) New clues for nephrotoxicity induced by ifosfamide: preferential renal uptake via the human organic cation transporter 2. Mol Pharm 8:270–279

    Article  CAS  PubMed  Google Scholar 

  • Cumberbatch MG, Rota M, Catto JW, La Vecchia C (2016) The role of tobacco smoke in bladder and kidney carcinogenesis: a comparison of exposures and meta-analysis of incidence and mortality risks. Eur Urol 70:458–466

    Article  CAS  PubMed  Google Scholar 

  • Dajani S, Saripalli A, Sharma-Walia N (2018) Water transport proteins-aquaporins (AQPs) in cancer biology. Oncotarget 9:36392–36405

    Article  PubMed  PubMed Central  Google Scholar 

  • Deckers IA, van den Brandt PA, van Engeland M, van Schooten FJ, Godschalk RW, Keszei AP, Hogervorst JG, Schouten LJ (2016) Potential role of gene-environment interactions in ion transport mechanisms in the etiology of renal cell cancer. Sci Rep 6:34262

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Delahunt B, Eble JN, Egevad L, Samaratunga H (2019) Grading of renal cell carcinoma. Histopathology 74:4–17

    Article  PubMed  Google Scholar 

  • Dy GW, Gore JL, Forouzanfar MH, Naghavi M, Fitzmaurice C (2017) Global burden of urologic cancers, 1990-2013. Eur Urol 71:437–446

    Article  PubMed  Google Scholar 

  • Edemir B, Pavenstadt H, Schlatter E, Weide T (2011) Mechanisms of cell polarity and aquaporin sorting in the nephron. Pflugers Arch 461:607–621

    Article  CAS  PubMed  Google Scholar 

  • El Hindy N, Bankfalvi A, Herring A, Adamzik M, Lambertz N, Zhu Y, Siffert W, Sure U, Sandalcioglu IE (2013) Correlation of aquaporin-1 water channel protein expression with tumor angiogenesis in human astrocytoma. Anticancer Res 33:609–613

    PubMed  Google Scholar 

  • Escudier B, Porta C, Schmidinger M, Rioux-Leclercq N, Bex A, Khoo V, Grunwald V, Gillessen S, Horwich A (2019) Renal cell carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-updagger. Ann Oncol 30:706–720

    Article  CAS  PubMed  Google Scholar 

  • Felmlee MA, Jones RS, Rodriguez-Cruz V, Follman KE, Morris ME (2020) Monocarboxylate transporters (SLC16): function, regulation, and role in health and disease. Pharmacol Rev 72:466–485

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fisel P, Kruck S, Winter S, Bedke J, Hennenlotter J, Nies AT, Scharpf M, Fend F, Stenzl A, Schwab M, Schaeffeler E (2013) DNA methylation of the SLC16A3 promoter regulates expression of the human lactate transporter MCT4 in renal cancer with consequences for clinical outcome. Clin Cancer Res 19:5170–5181

    Article  CAS  PubMed  Google Scholar 

  • Fisel P, Stuhler V, Bedke J, Winter S, Rausch S, Hennenlotter J, Nies AT, Stenzl A, Scharpf M, Fend F, Kruck S, Schwab M, Schaeffeler E (2015) MCT4 surpasses the prognostic relevance of the ancillary protein CD147 in clear cell renal cell carcinoma. Oncotarget 6:30615–30627

    Article  PubMed  PubMed Central  Google Scholar 

  • Hara-Chikuma M, Verkman AS (2008) Aquaporin-3 facilitates epidermal cell migration and proliferation during wound healing. J Mol Med 86:221–231

    Article  CAS  PubMed  Google Scholar 

  • Harlander S, Schönenberger D, Toussaint NC, Prummer M, Catalano A, Brandt L, Moch H, Wild PJ, Frew IJ (2017) Combined mutation in Vhl, Trp53 and Rb1 causes clear cell renal cell carcinoma in mice. Nat Med 23:869–877

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hidayat K, Du X, Zou SY, Shi BM (2017) Blood pressure and kidney cancer risk: meta-analysis of prospective studies. J Hypertens 35:1333–1344

    Article  CAS  PubMed  Google Scholar 

  • Hoerner CR, Chen VJ, Fan AC (2019) The 'Achilles Heel' of metabolism in renal cell carcinoma: Glutaminase inhibition as a rational treatment strategy. Kidney Cancer 3:15–29

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hudson CC, Liu M, Chiang GG, Otterness DM, Loomis DC, Kaper F, Giaccia AJ, Abraham RT (2002) Regulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycin. Mol Cell Biol 22:7004–7014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kobayashi M, Uematsu T, Tokura Y, Takei K, Sakamoto K, Narimatsu T, Nukui A, Kamai T (2019) Immunohistochemical expressionof sodium-dependent glucose transporter - 2 (SGLT-2) in clear cell renal carcinoma: possible prognostic implications. Int Braz J Urol 45:169–178

    Article  PubMed  PubMed Central  Google Scholar 

  • Koppes LL, Dekker JM, Hendriks HF, Bouter LM, Heine RJ (2005) Moderate alcohol consumption lowers the risk of type 2 diabetes: a meta-analysis of prospective observational studies. Diabetes Care 28:719–725

    Article  PubMed  Google Scholar 

  • Kourghi M, Pei JV, de Ieso ML, Nourmohammadi S, Chow PH, Yool AJ (2018) Fundamental structural and functional properties of aquaporin ion channels found across the kingdoms of life. Clin Exp Pharmacol Physiol 45:401–409

    Article  CAS  PubMed  Google Scholar 

  • Kreida S, Tornroth-Horsefield S (2015) Structural insights into aquaporin selectivity and regulation. Curr Opin Struct Biol 33:126–134

    Article  CAS  PubMed  Google Scholar 

  • Lee WK, Thevenod F (2019) Oncogenic PITX2 facilitates tumor cell drug resistance by inverse regulation of hOCT3/SLC22A3 and ABC drug transporters in colon and kidney cancers. Cancer Lett 449:237–251

    Article  CAS  PubMed  Google Scholar 

  • Lee JE, Hunter DJ, Spiegelman D, Adami HO, Albanes D, Bernstein L, van den Brandt PA, Buring JE, Cho E, Folsom AR, Freudenheim JL, Giovannucci E, Graham S, Horn-Ross PL, Leitzmann MF, Mccullough ML, Miller AB, Parker AS, Rodriguez C, Rohan TE, Schatzkin A, Schouten LJ, Virtanen M, Willett WC, Wolk A, Zhang SM, Smith-Warner SA (2007) Alcohol intake and renal cell cancer in a pooled analysis of 12 prospective studies. J Natl Cancer Inst 99:801–810

    Article  PubMed  Google Scholar 

  • Lee JW, Chou CL, Knepper MA (2015) Deep sequencing in microdissected renal tubules identifies nephron segment-specific transcriptomes. J Am Soc Nephrol 26:2669–2677

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu Y, Yang L, An H, Chang Y, Zhang W, Zhu Y, Xu L, Xu J (2015) High expression of solute carrier family 1, member 5 (SLC1A5) is associated with poor prognosis in clear-cell renal cell carcinoma. Sci Rep 5:16954

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu Y, Zheng X, Yu Q, Wang H, Tan F, Zhu Q, Yuan L, Jiang H, Yu L, Zeng S (2016) Epigenetic activation of the drug transporter OCT2 sensitizes renal cell carcinoma to oxaliplatin. Sci Trans Med 8:348ra97

    Google Scholar 

  • Lunt SY, van der Heiden MG (2011) Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu Rev Cell Dev Biol 27:441–464

    Article  CAS  PubMed  Google Scholar 

  • Maher ER (2018) Hereditary renal cell carcinoma syndromes: diagnosis, surveillance and management. World J Urol 36:1891–1898

    Article  PubMed  PubMed Central  Google Scholar 

  • Makhov P, Joshi S, Ghatalia P, Kutikov A, Uzzo RG, Kolenko VM (2018) Resistance to systemic therapies in clear cell renal cell carcinoma: mechanisms and management strategies. Mol Cancer Ther 17:1355–1364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marlar S, Jensen HH, Login FH, Nejsum LN (2017) Aquaporin-3 in cancer. Int J Mol Sci 18:2106

    Article  PubMed Central  CAS  Google Scholar 

  • Maugeri R, Schiera G, di Liegro CM, Fricano A, Iacopino DG, di Liegro I (2016) Aquaporins and brain tumors. Int J Mol Sci 17:1029

    Article  PubMed Central  CAS  Google Scholar 

  • Mazal PR, Stichenwirth M, Koller A, Blach S, Haitel A, Susani M (2005) Expression of aquaporins and PAX-2 compared to CD10 and cytokeratin 7 in renal neoplasms: a tissue microarray study. Mod Pathol 18:535–540

    Article  CAS  PubMed  Google Scholar 

  • Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G, Schreck RE, Abrams TJ, Ngai TJ, Lee LB, Murray LJ, Carver J, Chan E, Moss KG, Haznedar JO, Sukbuntherng J, Blake RA, Sun L, Tang C, Miller T, Shirazian S, Mcmahon G, Cherrington JM (2003) In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res 9:327–337

    CAS  PubMed  Google Scholar 

  • Mobasheri A, Marples D, Young IS, Floyd RV, Moskaluk CA, Frigeri A (2007) Distribution of the AQP4 water channel in normal human tissues: protein and tissue microarrays reveal expression in several new anatomical locations, including the prostate gland and seminal vesicles. Channels (Austin) 1:29–38

    Article  Google Scholar 

  • Moch H, Cubilla AL, Humphrey PA, Reuter VE, Ulbright TM (2016) The 2016 WHO classification of tumours of the urinary system and male genital organs-part A: renal, penile, and testicular Tumours. Eur Urol 70:93–105

    Article  PubMed  Google Scholar 

  • Morrissey KM, Stocker SL, Wittwer MB, Xu L, Giacomini KM (2013) Renal transporters in drug development. Annu Rev Pharmacol Toxicol 53:503–529

    Article  CAS  PubMed  Google Scholar 

  • Morrissey JJ, Mellnick VM, Luo J, Siegel MJ, Figenshau RS, Bhayani S, Kharasch ED (2015) Evaluation of urine Aquaporin-1 and Perilipin-2 concentrations as biomarkers to screen for renal cell carcinoma: A prospective Cohort study. JAMA Oncol 1:204–212

    Article  PubMed  PubMed Central  Google Scholar 

  • Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, Chen I, Bycott PW, Baum CM, Figlin RA (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356:115–124

    Article  CAS  PubMed  Google Scholar 

  • Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grunwald V, Thompson JA, Figlin RA, Hollaender N, Urbanowitz G, Berg WJ, Kay A, Lebwohl D, Ravaud A (2008) Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 372:449–456

    Article  CAS  PubMed  Google Scholar 

  • Motzer RJ, Escudier B, Mcdermott DF, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Procopio G, Plimack ER, Castellano D, Choueiri TK, Gurney H, Donskov F, Bono P, Wagstaff J, Gauler TC, Ueda T, Tomita Y, Schutz FA, Kollmannsberger C, Larkin J, Ravaud A, Simon JS, Xu LA, Waxman IM, Sharma P (2015) Nivolumab versus Everolimus in advanced renal-cell carcinoma. N Engl J Med 373:1803–1813

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Motzer RJ, Tannir NM, Mcdermott DF, Aren Frontera O, Melichar B, Choueiri TK, Plimack ER, Barthelemy P, Porta C, George S, Powles T, Donskov F, Neiman V, Kollmannsberger CK, Salman P, Gurney H, Hawkins R, Ravaud A, Grimm MO, Bracarda S, Barrios CH, Tomita Y, Castellano D, Rini BI, Chen AC, Mekan S, Mchenry MB, Wind-Rotolo M, Doan J, Sharma P, Hammers HJ, Escudier B (2018) Nivolumab plus Ipilimumab versus Sunitinib in advanced renal-cell carcinoma. N Engl J Med 378:1277–1290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Msaouel P, Hong AL, Mullen EA, Atkins MB, Walker CL, Lee CH, Carden MA, Genovese G, Linehan WM, Rao P, Merino MJ, Grodman H, Dome JS, Fernandez CV, Geller JI, Apolo AB, Daw NC, Hodges HC, Moxey-Mims M, Wei D, Bottaro DP, Staehler M, Karam JA, Rathmell WK, Tannir NM (2019) Updated recommendations on the diagnosis, management, and clinical trial eligibility criteria for patients with renal medullary carcinoma. Clin Genitourin Cancer 17:1–6

    Article  PubMed  Google Scholar 

  • Muglia VF, Prando A (2015) Renal cell carcinoma: histological classification and correlation with imaging findings. Radiol Bras 48:166–174

    Article  PubMed  PubMed Central  Google Scholar 

  • Nakanishi Y, Kitajima K, Yamada Y, Hashimoto T, Suzuki T, Go S, Kanematsu A, Nojima M, Yamakado K, Yamamoto S (2018) Diagnostic performance of (11)C-choline PET/CT and FDG PET/CT for staging and restaging of renal cell cancer. Ann Nucl Med 32:658–668

    Article  CAS  PubMed  Google Scholar 

  • Niu D, Kondo T, Nakazawa T, Kawasaki T, Yamane T, Mochizuki K, Kato Y, Matsuzaki T, Takata K, Katoh R (2012) Differential expression of aquaporins and its diagnostic utility in thyroid cancer. PLoS One 7:e40770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Noda Y, Sohara E, Ohta E, Sasaki S (2010) Aquaporins in kidney pathophysiology. Nat Rev Nephrol 6:168–178

    Article  CAS  PubMed  Google Scholar 

  • Ohe C, Smith SC, Sirohi D, Divatia M, De Peralta-Venturina M, Paner GP, Agaimy A, Amin MB, Argani P, Chen YB, Cheng L, Colecchia M, Comperat E, Werneck Da Cunha I, Epstein JI, Gill AJ, Hes O, Hirsch MS, Jochum W, Kunju LP, Maclean F, Magi-Galluzzi C, Mckenney JK, Mehra R, Nesi G, Osunkoya AO, Picken MM, Rao P, Reuter VE, De Oliveira Salles PG, Schultz L, Tickoo SK, Tomlins SA, Trpkov K, Amin MB (2018) Reappraisal of morphologic differences between renal medullary carcinoma, collecting duct carcinoma, and fumarate hydratase-deficient renal cell carcinoma. Am J Surg Pathol 42:279–292

    Article  PubMed  PubMed Central  Google Scholar 

  • Oswald S, Muller J, Neugebauer U, Schroter R, Herrmann E, Pavenstadt H, Ciarimboli G (2019) Protein abundance of clinically relevant drug transporters in the human kidneys. Int J Mol Sci 20:5303

    Article  CAS  PubMed Central  Google Scholar 

  • Parker MD, Myers EJ, Schelling JR (2015) Na+-H+ exchanger-1 (NHE1) regulation in kidney proximal tubule. Cell Mol Life Sci 72:2061–2074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perez-Escuredo J, van Hee VF, Sboarina M, Falces J, Payen VL, Pellerin L, Sonveaux P (2016) Monocarboxylate transporters in the brain and in cancer. Biochim Biophys Acta 1863:2481–2497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Peyromaure M, Misrai V, Thiounn N, Vieillefond A, Zerbib M, Flam TA, Debre B (2004) Chromophobe renal cell carcinoma: analysis of 61 cases. Cancer 100:1406–1410

    Article  PubMed  Google Scholar 

  • Rambow J, Wu B, Rönfeldt D, Beitz E (2014) Aquaporins with anion/monocarboxylate permeability: mechanisms, relevance for pathogen-host interactions. Front Pharmacol 5:199–199

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Reustle A, Fisel P, Renner O, Buttner F, Winter S, Rausch S, Kruck S, Nies AT, Hennenlotter J, Scharpf M, Fend F, Stenzl A, Bedke J, Schwab M, Schaeffeler E (2018) Characterization of the breast cancer resistance protein (BCRP/ABCG2) in clear cell renal cell carcinoma. Int J Cancer 143:3181–3193

    Article  CAS  PubMed  Google Scholar 

  • Rubenwolf PC, Otto W, Denzinger S, Hofstadter F, Wieland W, Georgopoulos NT (2014) Expression of aquaporin water channels in human urothelial carcinoma: correlation of AQP3 expression with tumour grade and stage. World J Urol 32:991–997

    Article  CAS  PubMed  Google Scholar 

  • Saadoun S, Papadopoulos MC, Hara-Chikuma M, Verkman AS (2005) Impairment of angiogenesis and cell migration by targeted aquaporin-1 gene disruption. Nature 434:786

    Article  CAS  PubMed  Google Scholar 

  • Saleeb RM, Farag M, Lichner Z, Brimo F, Bartlett J, Bjarnason G, Finelli A, Rontondo F, Downes MR, Yousef GM (2018a) Modulating ATP binding cassette transporters in papillary renal cell carcinoma type 2 enhances its response to targeted molecular therapy. Mol Oncol 12:1673–1688

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saleeb RM, Plant P, Tawedrous E, Krizova A, Brimo F, Evans AJ, Wala SJ, Bartlett J, Ding Q, Boles D, Rotando F, Farag M, Yousef GM (2018b) Integrated phenotypic/genotypic analysis of papillary renal cell carcinoma subtypes: identification of prognostic markers, cancer-related pathways, and implications for therapy. Eur Urol Focus 4:740–748

    Article  PubMed  Google Scholar 

  • Sarungbam J, Mehra R, Tomlins SA, Smith SC, Jayakumaran G, Al-Ahmadie H, Gopalan A, Sirintrapun SJ, Fine SW, Zhang Y, Amin MB, Reuter VE, Chen YB, Tickoo SK (2019) Tubulocystic renal cell carcinoma: a distinct clinicopathologic entity with a characteristic genomic profile. Mod Pathol 32:701–709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scalise M, Pochini L, Galluccio M, Console L, Indiveri C (2017) Glutamine transport and mitochondrial metabolism in Cancer cell growth. Front Oncol 7:306

    Article  PubMed  PubMed Central  Google Scholar 

  • Schaeffeler E, Hellerbrand C, Nies AT, Winter S, Kruck S, Hofmann U, van der Kuip H, Zanger UM, Koepsell H, Schwab M (2011) DNA methylation is associated with downregulation of the organic cation transporter OCT1 (SLC22A1) in human hepatocellular carcinoma. Genome Med 3:82

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schmidt LS, Linehan WM (2016) Genetic predisposition to kidney cancer. Semin Oncol 43:566–574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schönenberger D, Rajski M, Harlander S, Frew IJ (2016) Vhl deletion in renal epithelia causes HIF-1α-dependent, HIF-2α-independent angiogenesis and constitutive diuresis. Oncotarget 7:60971–60985

    Article  PubMed  PubMed Central  Google Scholar 

  • Schrödter S, Braun M, Syring I, Klümper N, Deng M, Schmidt D, Perner S, Müller SC, Ellinger J (2016) Identification of the dopamine transporter SLC6A3 as a biomarker for patients with renal cell carcinoma. Mol Cancer 15:10–10

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Shnitsar V, Eckardt R, Gupta S, Grottker J, Muller GA, Koepsell H, Burckhardt G, Hagos Y (2009) Expression of human organic cation transporter 3 in kidney carcinoma cell lines increases chemosensitivity to melphalan, irinotecan, and vincristine. Cancer Res 69:1494–1501

    Article  CAS  PubMed  Google Scholar 

  • Shuch B, Linehan WM, Srinivasan R (2013) Aerobic glycolysis: a novel target in kidney cancer. Expert Rev Anticancer Ther 13:711–719

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Siegsmund M, Brinkmann U, Schaffeler E, Weirich G, Schwab M, Eichelbaum M, Fritz P, Burk O, Decker J, Alken P, Rothenpieler U, Kerb R, Hoffmeyer S, Brauch H (2002) Association of the P-glycoprotein transporter MDR1(C3435T) polymorphism with the susceptibility to renal epithelial tumors. J Am Soc Nephrol 13:1847–1854

    Article  CAS  PubMed  Google Scholar 

  • Sigauke E, Rakheja D, Maddox DL, Hladik CL, White CL, Timmons CF, Raisanen J (2006) Absence of expression of SMARCB1/INI1 in malignant rhabdoid tumors of the central nervous system, kidneys and soft tissue: an immunohistochemical study with implications for diagnosis. Mod Pathol 19:717–725

    Article  CAS  PubMed  Google Scholar 

  • Sreedharan S, Petros JA, Master VA, Ogan K, Pattaras JG, Roberts DL, Lian F, Arnold RS (2014) Aquaporin-1 protein levels elevated in fresh urine of renal cell carcinoma patients: potential use for screening and classification of incidental renal lesions. Dis Markers 2014:6

    Article  CAS  Google Scholar 

  • Stock C, Pedersen SF (2017) Roles of pH and the Na(+)/H(+) exchanger NHE1 in cancer: from cell biology and animal models to an emerging translational perspective? Semin Cancer Biol 43:5–16

    Article  CAS  PubMed  Google Scholar 

  • Sui W, Matulay JT, Robins DJ, James MB, Onyeji IC, Roychoudhury A, Wenske S, Decastro GJ (2017) Collecting duct carcinoma of the kidney: disease characteristics and treatment outcomes from the National Cancer Database. Urol Oncol 35:540.e13–540.e18

    Article  Google Scholar 

  • Tang Z, Kang B, Li C, Chen T, Zhang Z (2019) GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res 47:W556–W560

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • The Cancer Genome Atlas Research, N (2013) Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature 499:43–49

    Article  CAS  Google Scholar 

  • Ticozzi-Valerio D, Raimondo F, Pitto M, Rocco F, Bosari S, Perego R, Sarto C, di Fonzo A, Bosso N, Mocarelli P, Galli-Kienle M, Magni F (2007) Differential expression of AQP1 in microdomain-enriched membranes of renal cell carcinoma. Proteomics Clin Appl 1:588–597

    Article  CAS  PubMed  Google Scholar 

  • Tie L, Lu N, Pan XY, Pan Y, An Y, Gao JW, Lin YH, Yu HM, Li XJ (2012) Hypoxia-induced up-regulation of aquaporin-1 protein in prostate cancer cells in a p38-dependent manner. Cell Physiol Biochem 29:269–280

    Article  CAS  PubMed  Google Scholar 

  • Tomita Y, Dorward H, Yool AJ, Smith E, Townsend AR, Price TJ, Hardingham JE (2017) Role of aquaporin 1 signalling in cancer development and progression. Int J Mol Sci 18:299

    Article  PubMed Central  CAS  Google Scholar 

  • Tsang SH, Sharma T (2018) Von Hippel-Lindau disease. Adv Exp Med Biol 1085:201–203

    Article  PubMed  Google Scholar 

  • Vallon V, Platt KA, Cunard R, Schroth J, Whaley J, Thomson SC, Koepsell H, Rieg T (2011) SGLT2 mediates glucose reabsorption in the early proximal tubule. J Am Soc Nephrol 22:104–112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Verrey F, Singer D, Ramadan T, Vuille-Dit-Bille RN, Mariotta L, Camargo SM (2009) Kidney amino acid transport. Pflugers Arch 458:53–60

    Article  CAS  PubMed  Google Scholar 

  • Visentin M, Torozi A, Gai Z, Hausler S, Li C, Hiller C, Schraml PH, Moch H, Kullak-Ublick GA (2018) Fluorocholine transport mediated by the organic cation transporter 2 (OCT2, SLC22A2): implication for imaging of kidney tumors. Drug Metab Dispos 46:1129–1136

    Article  CAS  PubMed  Google Scholar 

  • Wach S, Taubert H, Weigelt K, Hase N, Köhn M, Misiak D, Hüttelmaier S, Stöhr CG, Kahlmeyer A, Haller F, Vera J, Hartmann A, Wullich B, Lai X (2019) RNA sequencing of collecting duct renal cell carcinoma suggests an interaction between miRNA and target genes and a predominance of deregulated solute carrier genes. Cancers 12:64

    Article  PubMed Central  CAS  Google Scholar 

  • Wang G, Rao P (2018) Succinate dehydrogenase-deficient renal cell carcinoma: A short review. Arch Pathol Lab Med 142:1284–1288

    Article  CAS  PubMed  Google Scholar 

  • Wang F, Xu Y (2014) Body mass index and risk of renal cell cancer: a dose-response meta-analysis of published cohort studies. Int J Cancer 135:1673–1686

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Yin JY, Li XP, Chen J, Qian CY, Zheng Y, Fu YL, Chen ZY, Zhou HH, Liu ZQ (2014) The association of transporter genes polymorphisms and lung cancer chemotherapy response. PLoS One 9:e91967

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wang J, Feng L, Zhu Z, Zheng M, Wang D, Chen Z, Sun H (2015) Aquaporins as diagnostic and therapeutic targets in cancer: how far we are? J Transl Med 13:96

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Warren AY, Harrison D (2018) WHO/ISUP classification, grading and pathological staging of renal cell carcinoma: standards and controversies. World J Urol 36:1913–1926

    Article  PubMed  PubMed Central  Google Scholar 

  • Winter S, Fisel P, Buttner F, Rausch S, D'amico D, Hennenlotter J, Kruck S, Nies AT, Stenzl A, Junker K, Scharpf M, Hofmann U, VAN DER Kuip H, Fend F, Ott G, Agaimy A, Hartmann A, Bedke J, Schwab M, Schaeffeler E (2016) Methylomes of renal cell lines and tumors or metastases differ significantly with impact on pharmacogenes. Sci Rep 6:29930

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yin T, Yu S, Xiao L, Zhang J, Liu C, Lu Y, Liu C (2008) Correlation between the expression of aquaporin 1 and hypoxia-inducible factor 1 in breast cancer tissues. J Huazhong Univ Sci Technolog Med Sci 28:346–348

    Article  PubMed  Google Scholar 

  • Zhang S, Lovejoy KS, Shima JE, Lagpacan LL, Shu Y, Lapuk A, Chen Y, Komori T, Gray JW, Chen X, Lippard SJ, Giacomini KM (2006) Organic cation transporters are determinants of oxaliplatin cytotoxicity. Cancer Res 66:8847–8857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang J, Xiong Y, Lu LX, Wang H, Zhang YF, Fang F, Song YL, Jiang H (2013) AQP1 expression alterations affect morphology and water transport in Schwann cells and hypoxia-induced up-regulation of AQP1 occurs in a HIF-1alpha-dependent manner. Neuroscience 252:68–79

    Article  CAS  PubMed  Google Scholar 

  • Zhu L, Ma N, Wang B, Wang L, Zhou C, Yan Y, He J, Ren Y (2019) Significant prognostic values of aquaporin mRNA expression in breast cancer. Cancer Manag Res 11:1503–1515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zou LB, Zhang RJ, Tan YJ, Ding GL, Shi S, Zhang D, He RH, Liu AX, Wang TT, Leung PC, Sheng JZ, Huang HF (2011) Identification of estrogen response element in the aquaporin-2 gene that mediates estrogen-induced cell migration and invasion in human endometrial carcinoma. J Clin Endocrinol Metab 96:E1399–E1408

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medicine Clinic D, Experimental Nephrology, University Hospital of Münster, Münster, Germany

    Giuliano Ciarimboli

  2. Clinic of Urology, University Hospital, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany

    Gerit Theil & Joanna Bialek

  3. Department of Medicine, Hematology and Oncology, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany

    Bayram Edemir

Authors
  1. Giuliano Ciarimboli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gerit Theil
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joanna Bialek
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bayram Edemir
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bayram Edemir .

Editor information

Editors and Affiliations

  1. Medizinische Hochschule Hannover, Zentrum für Innere Medizin, Hannover, Germany

    Christian Stock

  2. Max-Planck-Institut für Experimentelle Medizin, Göttingen, Germany

    Luis A. Pardo

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Ciarimboli, G., Theil, G., Bialek, J., Edemir, B. (2020). Contribution and Expression of Organic Cation Transporters and Aquaporin Water Channels in Renal Cancer. In: Stock, C., Pardo, L.A. (eds) Transportome Malfunction in the Cancer Spectrum. Reviews of Physiology, Biochemistry and Pharmacology, vol 181. Springer, Cham. https://doi.org/10.1007/112_2020_34

Download citation

Publish with us

Policies and ethics

Search

Navigation