Transforming growth factor beta1 produced in autocrine/paracrine manner affects the morphology and function of mesothelial cells and promotes peritoneal carcinomatosis.
Transforming growth factor beta1 produced in autocrine/paracrine manner affects the morphology and function of mesothelial cells and promotes peritoneal carcinomatosis.
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以自分泌/旁分泌方式产生的转化生长因子β1影响间皮细胞的形态和功能并促进腹膜癌病。
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发表时间：
2010
影响因子：
5.4
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中科院分区：
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完整间皮中的人腹膜间皮细胞（HPMC）已被证明可以防止肿瘤腹膜转移。我们既往报道胃癌细胞可诱导腹膜凋亡，导致腹膜完整性受损，从而促进腹膜转移。在这项研究中，我们研究了 TGF-β1 对肿瘤-间皮相互作用的影响。简而言之，测量了各种可溶性因子，特别是TGF-β1的水平。 HMrSV5 细胞（一种人腹膜间皮细胞系）与 TGF-β1、胃癌细胞或胃癌细胞和 TGF-β1 受体抑制剂 SB431542 共孵育。评估了 smad 2/3 和磷酸化 smad 2/3（TGF-β/Smads 途径激活的指标）的表达。然后观察HPMCs的形态变化。通过荧光显微镜和流式细胞术定量测定细胞损伤。还检查了肿瘤-间皮细胞粘附。结果显示，间皮细胞与胃癌细胞系共培养后，TGF-β1 表达显着升高，同时磷酸化-smad 2/3 水平显着升高。此外，暴露于胃癌细胞或TGF-β1的间皮细胞会脱落并表现出损伤迹象，而阻断TGF-β1可以部分抑制这些作用。这些结果表明，腹膜腔中以自分泌/旁分泌方式产生的可溶性因子，例如TGF-β1，影响间皮细胞的形态和功能，从而产生有利于腹膜转移的环境。
Human peritoneal mesothelial cells (HPMCs) in intact mesothelium have been demonstrated to protect against tumor peritoneal metastasis. We have previously reported that gastric cancer cells can induce peritoneal apoptosis, lead to damage of peritoneum integrity, and therefore promote peritoneal metastasis. In this study, we investigated the effects of TGF-beta1 on tumor-mesothelial interaction. Briefly, the levels of various soluble factors, in particular TGF-beta1, were measured. HMrSV5 cells, a human peritoneal mesothelial cell line, were co-incubated with TGF-beta1, gastric cancer cells, or gastric cancer cells and TGF-beta1 receptor inhibitor SB431542. The expressions of smad 2/3 and phosphorylated smad 2/3, indicator of TGF-beta/Smads pathway activation, were evaluated. Then the morphological changes of HPMCs were observed. The cell damage was quantitatively determined by fluorescent microscopy and flow cytometry. Tumor-mesothelial cell adhesion was also examined. Results showed a significant elevation of TGF-beta1 expression, which is companied by dramatically increased phosphorylated-smad 2/3 levels, after mesothelial cell co-culture with the gastric cancer cell line. In addition, mesothelial cells exposed to gastric cancer cells or TGF-beta1 became exfoliated and exhibited signs of injury, while blocking TGF-beta1 can partially inhibit these effects. These results indicate that soluble factors, such as TGF-beta1, produced in autocrine/paracrine manner in the peritoneal cavity, affect the morphology and function of mesothelial cells so that the resulting environment becomes favorable for peritoneal metastases.