Zusammenfassung
Die Adipositas wird als ein möglicher Risikofaktor für viele Tumore diskutiert. Die vorliegende Übersicht befasst sich mit den aktuellen Erkenntnissen über den klinischen und biologischen Einfluss der Adipositas auf die Entstehung und Progression des Prostatakarzinoms, der Rolle der Fettgewebehormone (Adipozytokine) in diesem Szenario und den daraus möglicherweise ableitbaren klinischen Implikationen. Überdies werden die Ergebnisse eigener experimenteller und klinischer Untersuchungen über die Beteiligung von Adipozytokinen (Leptin, Adiponektin) in der Pathophysiologie des Prostatakarzinoms dargestellt. Dabei zeigte sich, dass Patienten, die an einem Prostatakarzinom erkranken, höhere Serumleptin- und niedrigere Adiponektinkonzentrationen hatten. Eigene und andere Studien zeigten ferner, dass höhere Serumspiegel des Leptins mit größeren Tumoren, High-grade-Klassifikationen, biochemischem Rezidiv, Metastasierung und Progression der metastasierten Tumoren sowie gesteigerter Mortalität einhergehen. Überdies korrelierte die Höhe des Plasmaleptins direkt mit dem PSA-Spiegel. Leptin stimulierte in vitro die Proliferation und hemmte die Apoptose der Prostatakarzinomzellen dosis- und zeitabhängig, wobei Androgen-resistente Zellen stärker reagierten.
Auf molekularer Ebene benötigten die Adipozytokine das Netzwerk der Tyrosinkinasen um ihre mitogenen und antiapoptotischen Effekte in Prostatakarzinomzellen zu bewerkstelligen. Prominente Mitglieder der wichtigsten Signaltransduktionskaskaden wie beispielsweise MAPK, PI3-K und JAK/STAT werden nach Bindung von Leptin an seinem Rezeptor an der Zellmembran der Prostatakarzinomzellen aktiviert. Adipozytokine wie Leptin können als zusätzliche Prognoseparameter zur Evaluierung bestimmter Therapien beim metastasierten hormonrefraktären Prostatakarzinom dienen. Die hier dargestellten Befunde sind als Grundlage für weiterführende Untersuchungen zu verstehen.
Abstract
Obesity is proposed as a possible risk factor for many tumors. The present review discusses the current knowledge on the clinical and biological impact of obesity on the development and progression of prostate cancer, the role of adipocyte-derived hormones (adipocytokines) in this scenario and the resulting clinical implications. In addition, the results of own experimental and clinical studies on the involvement of adipocytokines (e.g. leptin, adiponectin) in the pathophysiology of prostate cancer are presented. It was found that patients who were diagnosed with prostate cancer at this clinic had higher serum leptin and lower serum adiponectin concentrations. These investigations and other studies have further shown that higher serum levels of the adipocytokine leptin were associated with larger prostate cancer volumes, high-grade classification, biochemical recurrence, metastasis and progression of metastatic prostate tumors, as well as increased mortality. Moreover, there was a strong correlation between the serum level of leptin and serum levels of prostate specific antigen (PSA). Leptin stimulated in vitro the proliferation and inhibited the apoptosis of prostate cancer cells in a dose and time-dependent manner, however, androgen-resistant cell lines responded more strongly.
At the molecular level, adipocytokines require the network of tyrosine kinases to accomplish the mitogenic and antiapoptotic effects in prostate cancer cells. Prominent members of the most important signal transduction cascades, such as MAPK, PI3-K and JAK/STAT are activated upon binding of leptin to its receptor on the cell membrane of prostate cancer cells. Adipocytokines such as leptin may serve as additional prognostic parameters for the evaluation of specific therapies for metastatic hormone refractory prostate cancer. The findings presented here are intended as a basis for further studies.
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Hoda, M., Mohammed, N., Theil, G. et al. Übergewicht und Prostatakarzinom. Urologe 51, 1253–1260 (2012). https://doi.org/10.1007/s00120-012-2878-6
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DOI: https://doi.org/10.1007/s00120-012-2878-6