Hypoxia of PC-3 prostate cancer cells enhances migration and vasculogenesis in vitro of bone marrow-derived endothelial progenitor cells by secretion of cytokines

Abstract

Hypoxia is a key inducer of neovascularization which is essential for tumor growth, invasion and metastasis. It has been proposed that the recruitment of bone-marrow-derived endothelial progenitor cells (BM-EPCs) is pivotal and requires the participation of several tumor-derived cytokines. However, it is not known whether prostate cancer (PCa) cells contribute to the recruitment and vasculogenesis of EPCs in PCa progression. In the present study, we demonstrated that all conditioned medium (CM) of PC-3 PCa cells promoted proliferation and migration, and augmented the vasculogenesis capacity of BM-EPCs, and 24-h hypoxia (24H)-CM presented stronger ability compared to 24-h normoxia (24N)-CM and 48H-CM. Human cytokine antibody array with 174 anti-cytokine antibodies revealed the changes of cytokine in CMs. Twenty-five types of cytokines significantly increased in 24H-CM compared with 24N-CM. Eleven types of cytokines (5 factors increased and 6 decreased) were significantly different between 48H-CM and 48N-CM. Twelve types of cytokines (4 factors increased and 8 decreased) were significantly different between 48H-CM and 24H-CM. Furthermore, according to the Gene Ontology analysis, all altered cytokines were involved in proliferation, chemotaxis, cell motility, cell migration, vasculogenesis and angiogenesis. Of note, the changed regularity of cytokines in the 24H-CM and 48H-CM of PC-3 cells was in concert with the functional changes of BM-EPCs treated by different CM of PC-3 cells in enhancing the proliferation, migration and vasculogenesis potential of BM-EPCs. These findings suggest that PCa cells may have the potential to modulate their microenvironment and facilitate BM-EPC migration and vasculogenesis by secretion of cytokines in the early stage of hypoxia.