Tumour metastasis is a multi-factorial process and tumour cells are sensitive to local microenvironmental cues that regulate normal physiological functions such as wound healing and epithelial morphogenetic changes leading to malignant behaviour1. CD151, a member of the tetraspanin superfamily, has been identified in our laboratory as a promoter of prostate cancer (PCa) migration and invasion and involves association with integrins on both cell-cell and cell-stroma levels2, 3. Furthermore, CD151 plays a role in endothelial cell motility4-6. We investigated this protein further for its potential role in PCa metastasis.
CD151 is heterogeneously expressed across different PCa cell lines and the level of CD151 expression was significantly higher in the highly tumorigenic, androgen-insensitive cells PC-3 and DU-145 compared to the androgen-sensitive cell line LNCaP (P<0.001). This supports the previous findings by our laboratory7 that CD151 has value as a prognostic indicator for human PCa. Also, we found that CD151 has a role in the promotion of motility and invasion of PCa cell lines. Orthotopic implantation of human PC-3 cells into SCID mice prostate was investigated and the majority developed pelvic lymph node metastases. The level of CD151 expression in metastatic lesions was significantly increased compared to matched primary xenografts (P=0.04). Specimens from primary and secondary sites were investigated for CD31 (angiogenesis marker) expression; primary xenografts from mice forming secondary metastases had higher microvessel density (MVD) than xenografts from those without any metastases (P=0.029). MVD were not correlated with tumour size. These findings underscore the potential role of CD151 and angiogenesis in the metastatic potential of PCa, as suggested by a previous report in which CD151 knock-out animals had impaired pathologic angiogenesis8.
CD151 is likely to be an important regulator of cancer cell communication with the surrounding microenvironment, as an increase in tumor cell CD151 expression was associated with enhanced motility/metastasis and angiogenesis.