Protein-bound polysaccharide K suppresses tumor fibrosis in gastric cancer by inhibiting the TGF-β signaling pathway.
Protein-bound polysaccharide K suppresses tumor fibrosis in gastric cancer by inhibiting the TGF-β signaling pathway.
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DOI：
10.3892/or.2014.3636
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发表时间：
2015-02
期刊：
影响因子：
4.2
通讯作者：
Ohta T
中科院分区：
文献类型：
--
作者：
Shinbo T;Fushida S;Tsukada T;Harada S;Kinoshita J;Oyama K;Okamoto K;Ninomiya I;Takamura H;Kitagawa H;Fujimura T;Yashiro M;Hirakawa K;Ohta T
腹膜癌病（PC）是胃癌最常见的转移方式，其预后极差。 PC 的特征是丰富的纤维化和阻塞性疾病的发展，例如肠梗阻、黄疸和肾积水。上皮间质转化（EMT）是组织纤维化的主要原因之一，转化生长因子β（TGF-β）在EMT的进展中具有关键作用。蛋白结合多糖 K (PSK) 是一种生物反应调节剂，可以在体外调节 TGF-β/Smad 信号通路。在本研究中，我们使用人腹膜间皮细胞（HPMC）和人胃癌细胞系建立了纤维化肿瘤模型，以评估 PSK 是否减轻肿瘤纤维化。暴露于 PSK 的 HPMC 没有发生从鹅卵石状图案到通常由 TGF-β 处理诱导的纺锤形图案的形态变化。免疫荧光进一步证明 PSK 抑制 HPMC 中 TGF-β 诱导的 α-SMA 过度表达。我们通过使用小鼠异种移植模型进一步表明 HPMC 有助于肿瘤纤维化的增殖。此外，对这些小鼠进行 PSK 治疗显着减少了可观察到的肿瘤纤维化面积。这些结果表明，接种的癌细胞通过在微环境中释放TGF-β，将HPMC转化为肌成纤维细胞样细胞，促进HPMC覆盖的器官中纤维瘤的发展。因此，我们的研究表明 PSK 作为抗纤维化药物在治疗患有 PC 的胃癌患者中具有潜在的用途。
Peritoneal carcinomatosis (PC) is the most frequent metastatic pattern of gastric cancer and its prognosis is extremely poor. PC is characterized by rich fibrosis and the development of obstructive disorders such as ileus, jaundice and hydronephrosis. Epithelial-mesenchymal transition (EMT) is one of the major causes of tissue fibrosis and transforming growth factor β (TGF-β) has a pivotal function in the progression of EMT. Protein-bound polysaccharide K (PSK) is a biological response modifier that can modulate the TGF-β/Smad signaling pathway in vitro. In the present study, we established a fibrotic tumor model using human peritoneal mesothelial cells (HPMCs) and a human gastric cancer cell line to evaluate whether PSK attenuates tumor fibrosis. HPMCs exposed to PSK did not undergo the morphological change from a cobblestone-like pattern to a spindle-shape pattern normally induced by treatment with TGF-β. Immunofluorescence further demonstrated that PSK suppressed TGF-β-induced overexpression of α-SMA in the HPMCs. We further showed that HPMCs contributed to the proliferation of tumor fibrosis by using a mouse xenograft model. Additionally, PSK treatment of these mice significantly reduced the area of observable tumor fibrosis. These results suggest that seeded cancer cells transformed HPMCs into myofibroblast-like cells through their release of TGF-β in the microenvironment, facilitating the development of fibrous tumors in organs covered with HPMCs. Therefore, our study indicates that PSK has potential utility as an anti-fibrotic agent in the treatment of gastric cancer patients with PC.
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影响因子：
5.2
作者：
Tsukada T;Fushida S;Harada S;Terai S;Yagi Y;Kinoshita J;Oyama K;Tajima H;Ninomiya I;Fujimura T;Ohta T
通讯作者：
Ohta T
影响因子：
7.4
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
通讯作者：
Ohta, Tetsuo
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：
8.8
作者：
通讯作者：
--
影响因子：
5.7
作者：
Fuyuhiro, Yuhiko;Yashiro, Masakazu;Hirakawa, Kosei
通讯作者：
Hirakawa, Kosei