Bone marrow contribution to tumor-associated myofibroblasts and fibroblasts
Bone marrow contribution to tumor-associated myofibroblasts and fibroblasts
复制标题
DOI：
10.1158/0008-5472.can-04-1708
复制
发表时间：
2004-12-01
期刊：
影响因子：
11.2
通讯作者：
Wright, NA
中科院分区：
文献类型：
--
作者：
Direkze, NC;Hodivala-Dilke, K;Wright, NA
肌成纤维细胞在组织修复和纤维化中的作用已被充分证明，但这些肌成纤维细胞的来源尚不清楚。有证据表明，循环的纤维细胞群可以回到损伤区域，并有助于形成肌成纤维细胞群。以前，我们已经证明骨髓是许多组织（包括肠道、肺和肾）的肌成纤维细胞的来源，并且这种现象会因损伤而加剧。我们现在表明，在胰腺胰岛素瘤小鼠模型中，骨髓可以促进肿瘤基质中的肌成纤维细胞和成纤维细胞群。转入与SV40大t抗原（RIPTag）相关的大鼠胰岛素启动子II基因的小鼠发生胰腺实体β细胞肿瘤。这些胰腺肿瘤中约25%的肌成细胞是供体来源的，这些细胞集中在肿瘤边缘。因此，肿瘤基质的发展至少部分是一种系统性反应，最终可能产生靶向新疗法的方法。
The role of myofibroblasts in tissue repair and fibrosis is well documented, but the source of these myofibroblasts is unclear. There is evidence of a circulating population of fibrocytes that can home to areas of injury and contribute to myofibroblast populations. Previously, we have shown that the bone marrow is a source of myofibroblasts for many tissues including the gut, lung, and kidney and that this phenomenon is exacerbated by injury. We now show that the bone marrow can contribute to myofibroblast and fibroblast populations in tumor stroma in a mouse model of pancreatic insulinoma. Mice transgenic for the rat insulin promoter II gene linked to the large-T antigen of SV40 (RIPTag) develop solid beta-cell tumors of the pancreas. Approximately 25% of myoribroblasts in these pancreatic tumors were donor-derived, and these were concentrated toward the edge of the tumor. Thus, the development of tumor stroma is at least in part a systemic response that may ultimately yield methods of targeting new therapy.