It is well known that during ovarian cancer progression, the omentum transforms from a thin lacy organ to a thick tougher tissue. However, the mechanisms regulating this transformation and the implications of the altered microenvironment on ovarian cancer progression remain unclear. To address these questions, the global and local concentrations of collagen I were determined for normal and metastatic human omentum. Collagen I was increased 5.3-fold in omenta from ovarian cancer patients and localized to areas of activated fibroblasts rather than regions with a high density of cancer cells. Transforming growth factor beta 1 (TGFβ1) was detected in ascites from ovarian cancer patients (4 ng/mL), suggesting a potential role for TGFβ1 in the observed increase in collagen. Treatment with TGFβ1 induced fibroblast activation, proliferation, and collagen deposition in mouse omental explants and an in vitro model with human omental fibroblasts. Finally, the impact of increased collagen I on ovarian cancer cells was determined by examining proliferation on collagen I gels formulated to mimic normal and cancerous omenta. While collagen density alone had no impact on proliferation, a synergistic effect was observed with collagen density and heparin-binding epidermal growth factor treatment. These results suggest that TGFβ1 induces collagen deposition from the resident fibroblasts in the omentum and that this altered microenvironment impacts cancer cell response to growth factors found in ascites.

中文翻译：

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随着胶原蛋白密度的增加，卵巢细胞对肝素结合表皮生长因子的增殖也有所增加。

众所周知，在卵巢癌进展期间，网膜从薄的花边器官转变为较厚的坚韧组织。但是，调节这种转化的机制以及微环境改变对卵巢癌进展的影响尚不清楚。为了解决这些问题，确定了正常和转移性人类大网膜的胶原蛋白I的整体和局部浓度。卵巢癌患者的全麦胶原蛋白I含量增加了5.3倍，并位于活化的成纤维细胞区域​​，而不是癌细胞密度高的区域。在卵巢癌患者的腹水中检测到转化生长因子β1（TGFβ1）（4 ng / mL），表明TGFβ1在观察到的胶原蛋白增加中具有潜在作用。用TGFβ1处理可诱导成纤维细胞活化，增殖，人网膜成纤维细胞的体外模型。最后，通过检查配制为模仿正常和癌性全基因组的胶原蛋白I凝胶上的增殖来确定胶原蛋白I对卵巢癌细胞的影响。虽然单独的胶原蛋白密度对增殖没有影响，但是观察到胶原蛋白密度和肝素结合表皮生长因子治疗的协同作用。这些结果表明，TGFβ1诱导了网膜中驻留的成纤维细胞的胶原蛋白沉积，并且这种改变的微环境影响了癌细胞对腹水中发现的生长因子的反应。