VEGFR۱, miR-۱۹b, and miR-۹۲a as potential molecular targets in anti- angiogenic therapy of cancer

Background and Aim: Despite of the inducing source, endothelial cells (ECs) are key players in angiogenesis. Receiving the stimulating signal, they switch to activate a series of signaling pathways which results in creating a new network to supply oxygen and nutrition for the hypoxic site which can be a neoplasm or a wound. Beside reported beneficial, sever drawbacks of cancer anti-angiogenic therapy strategies necessitate detailed studies decoding specific features of the process in physiologic versus pathologic conditions. In the present study, we have investigated EC response to coculturing with normal human fibroblasts or A۵۴۹ tumor cells.Methods: Human Umbilical vein endothelial cells (HUVECs) were cocultured differentially with normal fibroblast/A۵۴۹ cells using transwell plates. After ۲۴ hrs gene expression changes of VEGF, VEGFR۱, VEGFR۲, and miR-۱۷-۹۲ cluster were evaluated using real-time RT PCR.Results: Our results indicated a significant decline in expression of coding genes in cocultured ECs in comparison with single cultured ECs, while VEGFR۱ significantly decreased in ECs cocultured with normal fibroblasts in comparison with A۵۴۹ cocultured ECs. Furthermore, ECs cocultured with A۵۴۹ revealed a significant increase in miR-۱۹b and miR-۹۲a expression, the antiangiogenic members of mir-۱۷-۹۲ cluster, in comparison to normal fibroblasts.Conclusion: Our results provide evidence of the advantage of using coculture systems in studying ECs function and specific response in the specified angiogenic environment which may be valuable in evaluating different features of anti-angiogenic anticancer strategies. Moreover, our results suggest VEGFR۱, miR-۱۹b, and miR-۹۲a as potential molecular targets in specific anti-angiogenic cancer therapy strategies, the precise mechanism of their action needs further studies.

کلیدواژه ها:

Endothelial cell ، Angiogenesis ، Coculture ، VEGFR۱ ، miR-۱۷-۹۲