In:
Journal of Cellular and Molecular Medicine, Wiley, Vol. 22, No. 12 ( 2018-12), p. 5909-5918
Abstract:
Although targeted therapy is usually the first‐line treatment for advanced renal cell carcinoma ( RCC ), some patients can experience drug resistance. Cancer stem cells are tumour‐initiating cells that play a vital role in drug resistance, metastasis and cancer relapse, while galectins (Gal) participate in tumour progression and drug resistance. However, the exact role of galectins in RCC stemness is yet unknown. In this study, we grew a subpopulation of RCC cells as tumour spheres with higher levels of stemness‐related genes, such as Oct4, Sox2 and Nanog. Among the Gal family, Gal‐3 in particular was highly expressed in RCC tumour spheres. To further investigate Gal‐3's role in the stemness of RCC , lentivirus‐mediated knockdown and overexpression of Gal‐3 in RCC cells were used to examine both in vitro and in vivo tumorigenicity. We further assessed Gal‐3 expression in RCC tissue microarray using immunohistochemistry. Upon suppressing Gal‐3 in parental RCC cells, invasion, colony formation, sphere‐forming ability, drug resistance and stemness‐related gene expression were all significantly decreased. Furthermore, CXCL 6, CXCL 7 and CXCR 2 were down‐regulated in Gal‐3‐knockdown tumour spheres, while CXCR 2 overexpression in Gal‐3‐knockdown RCC restored the ability of sphere formation. Gal‐3 overexpression in RCC promoted both in vitro and in vivo tumorigenicity, and its expression was correlated with CXCR 2 expression and tumour progression in clinical tissues. RCC patients with higher co‐expressions of Gal‐3 and CXCR 2 demonstrated a worse survival rate. These results indicate that highly expressed Gal‐3 may up‐regulate CXCR 2 to augment RCC stemness. Gal‐3 may be a prognostic and innovative target of combined therapy for treating RCC .
Type of Medium:
Online Resource
ISSN:
1582-1838
,
1582-4934
DOI:
10.1111/jcmm.2018.22.issue-12
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2076114-4
