Carcinoma-associated fibroblasts derive from mesothelial cells via mesothelial-to-mesenchymal transition in peritoneal metastasis

摘要: Peritoneal dissemination is a frequent metastatic route for cancers of the ovary and gastrointestinal tract. Tumour cells metastasize by attaching to invading through mesothelial cell (MC) monolayer that lines peritoneal cavity. Metastases are influenced carcinoma-associated fibroblasts (CAFs), population derives from different sources. Hence, we investigated whether MCs, mesothelial-mesenchymal transition (MMT), were source CAFs during carcinomatosis MMT affected adhesion invasion tumour cells. Biopsies patients with revealed presence myofibroblasts expressing markers in proximity carcinoma implants. Prominent new vessel formation was observed areas harbouring when compared tumour-free regions. The use mouse model confirmed myofibroblast conversion MCs increase angiogenesis at places Treatment omentum conditioned media cultures resulted phenotype changes reminiscent MMT. Adhesion experiments demonstrated enhanced binding cancer β1-integrin-dependent manner. Scanning electron microscopy imaging showed mostly due increased cell-cell interaction not mere matrix exposure. Invasion assays suggested reciprocal stimulation invasive capacity MCs. Our results demonstrate can derive metastasis. We suggest renders peritoneum more receptive attachment/invasion contributes secondary growth promoting its vascularization.