The
chemokine receptor CCR7 and its
ligands CCL19/21 mediate the
tumor mobility, invasion, and
metastasis (Wu et al. Curr Pharm Des. 15:742-57, 2009).
Hypoxia induced epithelial-to-mesenchymal transition (EMT) to facilitate the
tumor biology. Here, we addressed the roles of CCR7 in
epithelial ovarian carcinoma tissues and
hypoxia-induced serous papillary cystic
adenocarcinoma (SKOV-3) EMT. The expression level of CCR7
protein was analyzed by immunohistochemistry in 30 specimens of
epithelial ovarian carcinomas. Western blot was used to investigate the expression of
hypoxia-induced CCR7, HIF-1α, and EMT markers (N-cadherin, Snail, MMP-9). In addition, wound healing and Transwell assay were introduced to observe the capacity of migration and invasiveness. Our data showed CCR7 expression was observed in 22 cases of tissues and closely associated with
lymph node metastasis and FIGO stage (III + IV). At 6, 12, 24, and 36 h following
hypoxia, CCR7 and HIF-1α
proteins were both obviously upregulated in a time-dependent method, compared with normal
oxygen. In vitro, SKOV-3 expressed
N-cadherin, Snail, and MMP-9 once either CCL21 stimulation or
hypoxia induction, while
hypoxia accompanied with CCL21 induction exhibited strongest upregulation of
N-cadherin, Snail, and MMP-9
proteins. Besides, wound healing and Transwell assay further identified that
hypoxia with CCL21 stimulation can remarkably promote cell migration and invasiveness. Taken together, CCR7 can constitutively express in
epithelial ovarian carcinomas and be induced rapidly in response to
hypoxia, which indeed participates in EMT development and prompts the cell migration and invasion. Thus, this study suggested that the
epithelial ovarian cancer invasion and
metastasis can be inhibited by antagonizing CCR7.