Somatostatin and CXCR4 chemokine receptor expression in hepatocellular and cholangiocellular carcinomas: tumor capillaries as promising targets.

BACKGROUND:Hepatocellular (HCC) and cholangiocellular carcinomas (CCC) display an exceptionally poor prognosis. Especially for advanced disease no efficient standard therapy is currently available. Recently, somatostatin analogs have been evaluated for the treatment of HCC, however, with contradictory results. Besides, for both malignancies the chemokine receptor CXCR4 has been discussed as a possible new target structure. METHODS:Expression of somatostatin receptor subtypes 1, 2A, 3, 4, and 5, and of CXCR4 was evaluated in a total of 71 HCCs and 27 CCCs by immunohistochemistry using well-characterized novel monoclonal antibodies. RESULTS:In HCC tumor cells, frequency and intensity of expression of and CXCR4 were only low. CXCR4 was present in about 40% of the HCCs, although at a low intensity. and were detected in about 15%, 8%, and 5% of the HCC tumors, respectively. and CXCR4 expression was much higher in CCC than in HCC. CXCR4 and were present in 60% and 67% of the CCC samples, respectively, followed by and duanyu1942R5, which were detected in 30% and 11% of the tumors, respectively. Most notably, CXCR4 was intensely expressed on the tumor capillaries in about 50% of the HCCs and CCCs. CXCR4 expression on tumor vessels was associated with poor patient outcomes. CONCLUSIONS:CCC, but not HCC, may be suitable for treatments. Because of the predominant expression of pan-somatostatin analogs should be preferred. In both HCC and CCC, indirect targeting of tumors via the CXCR4-positive tumor capillaries may represent a promising additional therapeutic strategy.

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