The effect of kisspeptin-10 on angiogenesis and tumor growth

Background and Aim: Kisspeptins (kp) bind to a coupled-G protein receptor, GPR54 or KISS-1R, to perform a variety of functions including modulation of processes involving angiogenesis such as tumor metastasis and invasion of trophoblast. In this study the effects of kp-10, the most active kisspeptin, on angiogenesis and tumor growth have been evaluated. Methods: Human umbilical vein endothelial cells (HUVECs) were treated with 10-100 or 500 nM kp-10 for 24 hours. Tube formation was evaluated in these groups and compared with nontreated cells with Matrigel-precoated 24-well culture dishes. In addition, treated adipose-derived mesenchymal stem cells with 10-100 or 500 nM kp-10 and nontreated cells were transfused via the tail vein to melanoma tumor bearing C57BL/6 mice. After 24 hours, the mice were scarified and number of vessels in tumor sections was evaluated by immunohistochemistry. Tumor size was measured with caliper and tumor volume was estimated. Kruskal-Wallis and Mann-Whitney tests were used to determine the difference between the treated and non-treated groups. Results: The results showed that kp-10 significantly increased angiogenesis at 100 nM compared to the other groups both in vitro and in vivo . Moreover, a significant increase in the tumor growth was observed at 100 nM of kp-10 compared to other groups. Conclusion: Our data demonstrated that kp-10 increases angiogenesis in tumor tissue, which may lead to increase in tumor size.