CONICET | Buscador de Institutos y Recursos Humanos

Angiogenesis which plays a critical role in tumor growth and metastases is a very early event in the development of premalignant lesions induced by HPV in the cervical cancer (CC). It involves multiple processes including the secretion of angiogenic factors by tumor cell which increases in hypoxic conditions. The objective of this work was to gain insight into the signaling events involved in angiogenesis induced by hypoxic conditions in CC studying the possible role of p90 ribosomal S6 kinase (RSK). Beside the emerging role of RSK in cancer, few studies have investigated its implication in the cell response to hypoxia. We employed HMEC-1 cells, an immortalized cell line of human microvascular endothelial cells, and conditioned media (CMs) from cervical cancer Hela cells, to evaluate the effect on endothelial cells of the factors released by cervical cancer cells treated with cobalt chloride (CoCl2) as a hypoxia mimic in the presence and absence of RSK inhibitor SL0101. We first evaluated the number of endothelial cells by crystal violet staining and trypan blue dye exclusion assay. We observed that CMs from Hela cells treated with CoCl2 increases the number of endothelial cells. However, the inhibition of RSK signaling pathway in Hela cells attenuated the stimulatory effects of these cervical cancer cells under hypoxic conditions in the proliferation of HMEC-1 cells. In addition, we performed tube formation assays using Geltrex. HMEC-1 cells were seeded on geltrex and treated with the corresponding CMs. CMs from Hela cells incubated with CoCl2 induce the formation of tube-like structures in endothelial cells seeded on geltrex whereas the pre-treated of the cervical cancer cells with the inhibitor SL0101 reversed partially this effect. These results suggest that RSK has a novel role in angiogenesis induced by hypoxic conditions in CC.