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Involvement of angiopoietins in cancer progression in association with cancer cell--fibroblast interaction.

PURPOSE
The role of angiopoietins (ANGs) in cancer progression is a new field of research. We examined the patterns of expression of ANGs in human renal cancer tissues (n =12) and investigated their roles in cancer progression in vitro and in vivo.


METHODS AND RESULTS
In normal renal tissue, the expression of ANG-1 was apparent in the glomerular capillaries and podocytes as well as in the endothelial cells of vessels, whereas we observed no expression of ANG-2. In contrast, in tumor tissue, dense, diffuse expression of ANG-1 was apparent in the fibroblasts, but not in the cancer cells. Intense ANG-2 expression was observed in the cancer cells themselves as well as in the endothelial cells, where its expression was restricted to small vessels or neoplastic capillaries and not mature vessels. Secondly, we investigated the influence of fibroblasts on the production of angiopoietins in cancer cells, using the human renal cancer cell lines SN12 and SN-PM6 and a human dermal fibroblast cell line (HDF). We examined the in vitro production of angiopoietins in these cell lines, in either monoculture of each cell line or co-culture of cancer cells and fibroblasts. Immunohistochemical study demonstrated marked production of ANG-1 in fibroblasts and ANG-2 expression in cancer cells when we performed co-culture, but no expression of either in each monoculture. Western blot analysis confirmed these results, showing marked expression of ANGs in co-cultured cells, but not in each monoculture.


CONCLUSION
Fibroblasts may influence cancer progression by promoting neoplastic angiogenesis, and ANGs are profoundly involved in this process through their association with the carcinoma cell-fibroblast interaction.