在全世界范围内，胃癌是恶性疾病中第二位常见的致死病因。然而，利物浦大学的新研究发现，通过恢复TGFβig-h3蛋白的功能，可能有助于未来胃癌治疗新手段的开发。利物浦大学的科学家发现，在胃癌患者体内，一种可以防止肿瘤细胞生长和播散的蛋白，其生成情况受到了损害。

　　该蛋白是由肌纤维母细胞释放的，此类细胞部分构成了癌细胞周边的支持组织。肌纤维母细胞、血管及其他类型细胞，其质量占整个瘤体质量的70%-90%，是癌细胞赖以存活的周边环境。

　　肌纤维母细胞是具有高度活动性的细胞，它可以产生并释放多种物质，通过改变肿瘤的周边环境，改变肿瘤的行为学，导致癌细胞生长和播散。利物浦大学的科学家发现，在晚期胃癌患者的肿瘤瘤体中，由肌纤维母细胞所释放的、正常状态下能够抑制肿瘤生长和播散的蛋白，其生成量减少了。

　　“在正常状态下，上述蛋白可以将癌细胞和其周边环境中的多种蛋白固定在一起，使得癌细胞与其适宜生长的环境隔绝开来。这种蛋白可作为靶向治疗的靶点，但在晚期癌症患者中，该蛋白效应减弱，以致肿瘤向身体其他部位转移的风险增高了。”利物浦大学转化医学研究所的Andrea Varro教授解释道，“我们希望，通过上述蛋白的功能恢复，在未来可以开发出新的治疗手段，继而有助于使罹患胃癌这种常见致死性疾病的患者达到长期康复。”

　　Release of TGFβig-h3 by gastric myofibroblasts slows tumor growth and is decreased with cancer progression.

　　Carcinogenesis 2012 Aug;33(8):1553-62 PMID:22610072

　　Holmberg C,Quante M,Steele I,Kumar JD,Balabanova S,Duval C,Czepan M,Rakonczay Z Jr,Tiszlavicz L,Nemeth I,Lazar G,Simonka Z,Jenkins R,Hegyi P,Wang TC,Dockray **,Varro A

　　Department of Cellular & Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.

　　Myofibroblasts; Stomach; Transforming Growth Factors

　　Tumor progression has been linked to changes in the stromal environment. Myofibroblasts are stromal cells that are often increased in tumors but their contribution to cancer progression is not well understood. Here, we show that the secretomes of myofibroblasts derived from gastric cancers [cancer-associated myofibroblasts (CAMs)] differ in a functionally significant manner from those derived from adjacent tissue [adjacent tissue myofibroblasts (ATMs)]. CAMs showed increased rates of migration and proliferation compared with ATMs or normal tissue myofibroblasts (NTMs). Moreover, conditioned medium (CM) from CAMs significantly stimulated migration, invasion and proliferation of gastric cancer cells compared with CM from ATMs or NTMs. Proteomic analysis of myofibroblast secretomes revealed decreased abundance of the extracellular matrix (ECM) adaptor protein like transforming growth factor-β-induced gene-h3 (TGFβig-h3) in CAMs, which was correlated with lymph node involvement and shorter survival. TGFβig-h3 inhibited IGF-II-stimulated migration and proliferation of both cancer cells and myofibroblasts, and suppressed IGF-II activation of p42/44 MAPkinase; TGFβig-h3 knockdown increased IGF-II- and CM-stimulated migration. Furthermore, administration of TGFβig-h3 inhibited myofibroblast-stimulated growth of gastric cancer xenografts. We conclude that stromal cells exert inhibitory as well as stimulatory effects on tumor cells; TGFβig-h3 is a stromal inhibitory factor that is decreased with progression of gastric cancers.