Vasohibin-1 and vasohibin-2 expression in gastric cancer cells and TAMs

Accumulating evidence suggests that TAMs contribute to tumor progression. Recently, vasohibin-1 and vasohibin-2 were detected in endothelial cells and considered as intrinsic angiogenesis inhibitors. However, it is not known whether they are also expressed in cancer cells or tumor-associated macrophages (TAMs). Realtime RT-PCR was used to investigate the vasohibin-1 and vasohibin-2 expression in four gastric cancer cell lines, including a non-metastatic cell line AGS, and metastatic cell lines HGC-27, Hs-746T and NCI-N87, co-cultured with or without TAMs. The effect of hypoxic conditions on vasohibin expression was evaluated as well, and the correlation between vasohibin-1, vasohibin-2 and VEGF-A expression under different culture conditions was analyzed. We found that both vasohibin-1 and vasohibin-2 were expressed in the four gastric cancer cell lines and in TAMs. Under normal conditions, vasohibin-1 and vasohibin-2 expressions were significantly upregulated by TAMs in all the gastric cancer cell lines. Under hypoxia, both vasohibin-1 and vasohibin-2 expressions were significantly decreased in the distant metastasis cancer cell line Hs-746T, cultured with or without TAMs (P < 0.001). After induction by TAMs or hypoxia, the vasohibin-1 and vasohibin-2 expressions correlated with that of VEGF-A. In addition, TAMs, when co-cultured with the metastatic cancer cell lines, showed hypoxia-induced vasohibin-1 upregulation (P < 0.05). In conclusion, both vasohibin-1 and vasohibin-2 mRNA are expressed in gastric cancer cells and in TAMs, and their expressions are altered by hypoxia.