![]() Recently, growing evidence suggested that cancers are not solely considered as core neoplastic cells, but as a dynamic crosstalk with the milieu of the tumors. ![]() Therefore, the metastatic and recurrence mechanisms of OvCA need to be profoundly elucidated. Approximately 90% of cases are of epithelial ovarian cancer (EOC) characterized by dissemination and metastasis. ![]() Despite traditional debulking surgery combined with chemotherapy and adjuvant therapies, 75% of patients develop advanced-stage (III–IV) with a low 5-year survival rate and recurrence within 3 years. Ovarian cancer (OvCA) is a leading fatal gynecologic malignancy worldwide. Our finding has provided a novel therapeutic clue for OvCA based on TME. Inhibition of the CRMP2 derived from CAFs by neutralizing antibodies significantly attenuated the tumor size, weights, and metastatic foci numbers of mice in vivo. The CRMP2 was abundantly expressed in OvCA, with a well correlation with metastasis and poor prognosis, as analyzed from 118 patients’ samples. In vitro study using recombinant CRMP2 (r-CRMP2) revealed that the protein promoted proliferation, invasion, and migration of OvCA cells through activation of hypoxia-inducible factor (HIF)-1α-glycolysis signaling pathway. Mass spectrum (MS) analysis identified that Collapsin response mediator protein-2 (CRMP2), a microtubule-associated protein involved in diverse malignancies, derived from CAFs was a key regulator responsible for mediating these cell events of OvCA. In the present study, the conditioned medium of primary CAFs (CAF-CM) from OvCA was used to culture cell lines of epithelial ovarian cancer (EOC), and showed a potent role in promoting proliferation, migration and invasion of cancer cells. However, less is known about the regulatory mechanism of CAFs on promoting progression of ovarian cancer (OvCA). As the predominant stroma cells of tumor microenvironment (TME), cancer associated fibroblasts (CAFs) are robust tumor player of different malignancies.
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