Similar to prostate cancer where expression OATP1B3 is significantly related to the Gleason score as a marker for tissue dedifferentiation [5], higher OATP1B3 levels in colon are associated with earlier tumor stage and they are found in better differentiated tumors. However, they are not predictive for the 5-year survival and for tumor recurrence. Within lower Inhibitors,research,lifescience,medical tumor grades, OATP1B3 expression is associated with an improved 5-year survival, while the tumor recurrence in patients with poorly differentiated tumors is LB42708? independent on
the expression of this OATP [16]. 7. OATP Expression in Pancreatic Cancer Extensive research has failed to produce any therapy efficient enough to substantially extend the median survival of treated patients beyond 6 months. Currently available therapies remain palliative on their intent [33–35]. Therefore, identification of new molecular targets and discovery of novel targeted therapies is of top priority for pancreatic cancer research. In a recent study, the expression of OATP1A2,
Inhibitors,research,lifescience,medical OATP1B1, and OATP1B3 was studied by immunohistochemistry in a sample of 12 patients as well as on the mRNA level in two pancreatic cancer cell lines [17]. Quantitative analysis was done by the Inhibitors,research,lifescience,medical HistoQUEST Software using the TissueFaxs Microscopic Image Analysis System (TissueGnostics, Inhibitors,research,lifescience,medical Vienna, Austria). The three studied polypeptides were found ubiquitously expressed in all studied pancreatic cancer biopsy samples. Methods used confirmed extensive immunostaining of the entire cancer cell tissue with the antibodies against these OATPs. In detail, the OATP1A2 expression signal was weak in one sample and moderate to strong in all others. OATP1B1 was found to be weakly expressed in all 12 cases. Immunostaining with the mMDQ antibody against OATP 1B1/1B3 was proved to be the most intense. Nine cases demonstrated moderate expression and three cases stained strong. OATP 1B1 and 1B3 mRNA expression Inhibitors,research,lifescience,medical in
two cell lines, MIA PaCa-2 and Bx-PC3, was comparable to that in normal liver, which was taken as a control, Brefeldin_A because both of these transporters are considered “liver-specific”. Their mRNA expression, however, in normal pancreas was either undetectable (OATP 1B1) or 30–60 times lower than that in normal liver (OATP 1B3). The OATPs investigated in this study were all found to be ubiquitously expressed at the protein and the mRNA level which flags them as appropriate candidates for in vitro studying of OATP-targeted anticancer compounds [17]. 8. OATP Expression in Liver Cancer In tumors of the liver, the expression of OATP1B1 and OATP1B3 is reduced along the degree of tissue dedifferentiation. This could reflect the reduction of metabolic function of liver cells in more advanced tumors [5].