Background and purpose: Ovarian cancer-associated fibroblasts (CAF) are known to promote epithelial malignancy. The chemoattractant cytokine growth-regulated oncogene alpha (Gro-α) secreted from CAF has been reported to mediate the stroma-epithelia interaction in tumor microenvironment

leading to the development of epithelial ovarian cancer

however

the detailed mechanism is unknown.This study was to determine whether Gro-α could promote ovarian tumorigenesis through activating NF-кB nuclear translocation and VEGF expression in stromal fibroblasts. Methods: ELISA was used to measure the levels of Gro-α in two cancer-associated fibroblasts (CAF) and normal fibroblasts (NF) isolated from high-grade serous ovarian cancer or normal ovarian tissues. CAF conditioned medium (CM) or Gro-α was used to treat NF

while PS1145

the inhibitor of NF-кB

was used as control. NF-кB subunit p65 and vascular endothelial growth factor (VEGF) were detected by Western blot in cells after treatment. Xenograft tumors from nude mice were generated by injection of CAF

NF

or OVCA429 alone or OVCA429 mixed with CAF or NF

and by injection of OVCA429 mixed with NF cells that were treated with or without CAF-CM or Gro-α

or with NF cells that were treated with CAF-CM or Gro-α plus PS1145. The tumor growth curve was measured and the blood vessel density in xenograft tumor tissues was examined by histopathological analysis. Results: The levels of Gro-α were 5-6 folds higher in CAF than in NF. Treatment of NF with CAF-CM or Gro-α stimulated the nuclear translocation of NF-кB subunit p65

and the expression of VEGF

but suppressed the expression of thrombospondin 1

the antiangiogenesis factor

compared with control cells. However

treatment of NF with the NF-кB inhibitor PS1145 reversed these results. The animal assay revealed that CAF stimulated tumor growth stronger than NF

and NF treated with CAF-CM or Gro-α

but not along with PS1145

enhanced xenograft tumor growth through promoting angiogenesis. Conclusion: Ovarian CAF promotes the nuclear translocation of NF-кB and the expression of VEGF through Gro-α autocrine in tumor microenvironment to facilitate angiogenesis and ovarian cancer development.