Abstract
The organic anion transporting polypeptide (OATP) family of transporters has been implicated in prostate cancer disease progression probably by transporting hormones or drugs. In this study, we aimed to elucidate the expression, frequency, and relevance of OATPs as a biomarker in hormone-dependent cancers. We completed a study examining SLCO1B3, SLCO1B1 and SLCO2B1 mRNA expression in 381 primary, independent patient samples representing 21 cancers and normal tissues. From a separate cohort, protein expression of OATP1B3 was examined in prostate, colon, and bladder tissue. Based on expression frequency, SLCO2B1 was lower in liver cancer (P = 0.04) which also trended lower with decreasing differentiation (P = 0.004) and lower magnitude in pancreatic cancer (P = 0.05). SLCO2B1 also had a higher frequency in thyroid cancer (67%) than normal (0%) and expression increased with stage (P = 0.04). SLCO1B3 was expressed in 52% of cancerous prostate samples and increased SLCO1B3 expression trended with higher Gleason score (P = 0.03). SLCO1B3 expression was also higher in testicular cancer (P = 0.02). SLCO1B1 expression was lower in liver cancer (P = 0.04) which trended lower with liver cancer grade (P = 0.0004) and higher with colon cancer grade (P = 0.05). Protein expression of OATP1B3 was examined in normal and cancerous prostate, colon, and bladder tissue samples from an independent cohort. The results were similar to the transcription data, but showed distinct localization. OATPs correlate to differentiation in certain hormone-dependent cancers, thus may be useful as biomarkers for assessing clinical treatment and stage of disease.
Highlights
Organic anion-transporting polypeptides (OATPs; encoded by SLCO genes) are involved in hepatocyte influx mechanisms and are overexpressed in some cancers [1,2,3]
OATP1B3 influx mechanisms are still unknown in colon cancer, there is sufficient evidence suggesting that OATP1B3 is overexpressed in a large proportion of colon tumors, and that this overexpression contributes to cell survival in the presence of oxalaplatin and camptothecin; the latter effect may be related to p53 expression [2]
SLCO overexpression has already been shown to be an important factor in colon and prostate cancer (1,2); variation in OATP function [1] appears to be related to clinical outcome of endocrine therapy in prostate cancer [5] as well as overall survival of men castration resistant prostate cancer (CRPC) [1]
Summary
Organic anion-transporting polypeptides (OATPs; encoded by SLCO genes) are involved in hepatocyte influx mechanisms and are overexpressed in some cancers [1,2,3]. Expression and genetic variation in OATPs have been associated with clinical outcomes in patients with prostate cancer Both SLCO1B3 and SLCO2B1 have been related to a shorter time to androgen deprivation therapy failure and decreased overall survival in patients with hormone responsive prostate cancer, and castration resistant prostate cancer (CRPC) respectively [1,5,6]. These associations might be attributed to genetic variation in androgen (or other steroid hormone) influx mechanisms that increase androgen scavenging during androgen deprivation therapy (ADT) [1]. OATP1B3 influx mechanisms are still unknown in colon cancer, there is sufficient evidence suggesting that OATP1B3 is overexpressed in a large proportion of colon tumors, and that this overexpression contributes to cell survival in the presence of oxalaplatin and camptothecin; the latter effect may be related to p53 expression [2]
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