Bone marrow derived "fibrocytes" contribute to tumor proliferation and fibrosis in gastric cancer.
Bone marrow derived "fibrocytes" contribute to tumor proliferation and fibrosis in gastric cancer.
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DOI：
10.1007/s10120-014-0380-0
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发表时间：
2015-04
期刊：
影响因子：
7.4
通讯作者：
Ohta, Tetsuo
中科院分区：
文献类型：
--
作者：
Terai, Shiro;Fushida, Sachio;Tsukada, Tomoya;Kinoshita, Jun;Oyama, Katsunobu;Okamoto, Koichi;Makino, Isamu;Tajima, Hidehiro;Ninomiya, Itasu;Fujimura, Takashi;Harada, Shinichi;Ohta, Tetsuo
肿瘤间质中的肿瘤相关成纤维细胞(CAF)被认为在胃癌的增殖、侵袭和纤维化中起重要作用，但CAF的来源及其在微环境中与癌细胞的相互作用尚未完全确定。在这里，我们阐明了骨髓来源的细胞，即纤维细胞，在以硬化性胃癌为代表的胃癌的发展中所起的作用。用免疫印迹法检测MKN45胃癌细胞与健康志愿者纯化的纤维细胞共培养过程中迁移和内皮间充质转化相关基因的表达。此外，我们还建立了MKN45小鼠移植瘤模型，观察其成瘤性和肿瘤免疫组织学差异。MKN45与成纤维细胞共培养后，细胞形态由鹅卵石状变为梭形，α-SMA和I型胶原表达增强，提示与胃癌细胞共培养可能诱导成纤维细胞向肌成纤维细胞分化。此外，还检测到SDF-1在MKN45和CXCR4在纤维细胞中的表达增强。接种MKN45和纤维细胞的小鼠移植瘤明显大于单独接种MKN45细胞的移植瘤，并且联合接种的肿瘤间质由肌成纤维细胞和纤维化组成。在共同接种的肿瘤中，也观察到表达CD45和I型胶原的小鼠来源细胞。骨髓来源的纤维细胞可能通过SDF-1/CXCR4系统向胃癌微环境迁移，与CAF一样促进肿瘤的增殖和纤维化。
Cancer-associated fibroblasts (CAFs) in the stroma are considered to play important roles for gastric cancer proliferation, invasion, and fibrosis, but the source of CAFs and their interaction with cancer cells in the microenvironment have not been fully determined. Here we elucidated the role of bone marrow-derived cells, fibrocytes, in development of gastric cancers, as represented by scirrhous gastric cancer. In co-culturing MKN45 gastric cancer cells and purified fibrocytes from healthy volunteers, migration and endothelial mesenchymal transition associated gene expression were evaluated using western blot analysis. Also, mouse xenograft models of MKN45 with or without fibrocytes were conducted to investigate their tumorigenicity and immunohistological differences of tumors. Co-culture of fibrocytes with MKN45 resulted in morphological changes from cobblestone-shape to spindle-shape and enhanced expression of α-SMA and collagen type I in fibrocytes, suggesting that co-culture with gastric cancer cells may have induced the differentiation of fibrocytes to myofibroblasts. Furthermore, enhanced expression of SDF-1 in MKN45 and CXCR4 in fibrocytes were also determined. Mouse xenograft models inoculated with MKN45 and fibrocytes revealed significantly larger tumors than those inoculated with MKN45 cells alone, and the stroma in co-inoculated tumors consisted of myofibroblasts and fibrosis. Mouse-derived cells expressing both CD45 and type I collagen were also observed in co-inoculated tumors. Fibrocytes derived from bone marrow may migrate into the microenvironment of gastric cancer by SDF-1/CXCR4 system, and enhance the tumor proliferation and fibrosis as CAFs.
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影响因子：
5.2
作者：
Tsukada T;Fushida S;Harada S;Yagi Y;Kinoshita J;Oyama K;Tajima H;Fujita H;Ninomiya I;Fujimura T;Ohta T
通讯作者：
Ohta T
影响因子：
3.3
作者：
Sakai, Norihiko;Furuichi, Kengo;Wada, Takashi
通讯作者：
Wada, Takashi
影响因子：
14.5
作者：
Tlsty, TD
通讯作者：
Tlsty, TD
影响因子：
4.8
作者：
Hong, Kurt M.;Belperio, John A.;Strieter, Robert M.
通讯作者：
Strieter, Robert M.
DOI：
10.1186/1756-9966-29-66
发表时间：
2010-06-08
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Zhi K;Shen X;Zhang H;Bi J
通讯作者：
Bi J