Wide peritoneal metastasis is the cause of the highest lethality of ovarian cancer in gynecologic malignancies. Ascites play a key role in ovarian cancer metastasis, but involved mechanism is uncertain. Here, we performed a quantitative proteomics of ascites, and found that collagen type I alpha 1 (COL1A1) was notably elevated in ascites from epithelial ovarian cancer patients compared to normal peritoneal fluids, and verified that elevated COL1A1 was mainly originated from fibroblasts. COL1A1 promoted migration and invasion of ovarian cancer cells, but such effects were partially eliminated by COL1A1 antibodies. Intraperitoneally injected COL1A1 accelerated intraperitoneal metastasis of ovarian cancer xenograft in NOD/SCID mice. Further, COL1A1 activated downstream AKT phosphorylation by binding to membrane surface receptor integrin β1 (ITGB1). Knockdown or blockage of ITGB1 reversed COL1A1 enhanced migration and invasion in ovarian cancer cells. Conversely, ovarian cancer ascites and fibrinogen promoted fibroblasts to secrete COL1A1. Elevated fibrinogen in ascites might be associated with increased vascular permeability induced by ovarian cancer. Our findings suggest that microenvironment remodeled by tumor cells and stromal cells promotes fibroblasts to secrete COL1A1 and facilitates the metastasis of ovarian cancer, which may provide a new approach for ovarian cancer therapeutics.

广泛的腹膜转移是妇科恶性肿瘤中卵巢癌致死率最高的原因。腹水在卵巢癌转移中起关键作用，但其参与机制尚不确定。在这里，我们进行了腹水的定量蛋白质组学研究，发现与正常腹膜液相比，上皮性卵巢癌患者腹水中的I型胶原1α1（COL1A1）明显升高，并证实了COL1A1升高主要来自成纤维细胞。COL1A1促进卵巢癌细胞的迁移和侵袭，但这种作用被COL1A1抗体部分消除。腹腔注射COL1A1加速了NOD / SCID小鼠卵巢癌异种移植的腹膜内转移。此外，COL1A1通过与膜表面受体整合素β1（ITGB1）结合来激活下游AKT磷酸化。击倒或阻断ITGB1可逆转COL1A1增强卵巢癌细胞的迁移和侵袭。相反，卵巢癌腹水和纤维蛋白原促进成纤维细胞分泌COL1A1。腹水中纤维蛋白原升高可能与卵巢癌引起的血管通透性增加有关。我们的发现表明，由肿瘤细胞和基质细胞重塑的微环境促进成纤维细胞分泌COL1A1并促进卵巢癌的转移，这可能为卵巢癌治疗提供了一种新方法。