Bagley Rebecca G, Weber William, Rouleau Cecile, Yao Min, Honma Nakayuki, Kataoka Shiro, Ishida Isao, Roberts Bruce L, Teicher Beverly A
Genzyme Corporation, Framingham, MA 01701-9322, USA.
Int J Oncol. 2009 Mar;34(3):619-27. doi: 10.3892/ijo_00000187.
Tumor development is a complex and dynamic process that involves malignant, vascular, and stromal cells. Endosialin is a tumor endothelial marker (TEM) present in the microvasculature and stroma of human tumors. Cancer-associated fibroblasts (CAF) have been implicated in promoting tumor development and have been associated with mesenchymal stem cells (MSC). Since stem/progenitor cells recruited either from bone marrow or residing in nearby tissues can contribute to pathological processes we investigated endosialin in MSC using a novel monoclonal antibody. Endosialin is highly expressed by CAF and human bone marrow-derived MSC. MSC can form networks in a tube formation assay that is inhibited by an anti-endosialin antibody. Immunohistochemistry for human endosialin in xenograft tumors following co-injection of MSC and cancer cells identified MSC in tumor stroma. MSC are a potential target for anticancer therapeutic intervention and endosialin expression offers a new tool for the identification of MSC. Endosialin expression by both CAF and MSC further implies the potential contribution of MSC to tumor stroma via differentiation into tumor stromal fibroblasts.
肿瘤发展是一个复杂且动态的过程,涉及恶性细胞、血管细胞和基质细胞。内涎蛋白是一种存在于人类肿瘤微血管和基质中的肿瘤内皮标志物(TEM)。癌症相关成纤维细胞(CAF)与促进肿瘤发展有关,且与间充质干细胞(MSC)相关。由于从骨髓募集或存在于附近组织中的干/祖细胞可参与病理过程,我们使用一种新型单克隆抗体研究了MSC中的内涎蛋白。CAF和人骨髓来源的MSC高度表达内涎蛋白。在一种管形成试验中,MSC可形成网络,而这种网络会被抗内涎蛋白抗体抑制。在共注射MSC和癌细胞后,对异种移植肿瘤中的人内涎蛋白进行免疫组织化学分析,在肿瘤基质中鉴定出了MSC。MSC是抗癌治疗干预的一个潜在靶点,内涎蛋白表达为鉴定MSC提供了一种新工具。CAF和MSC均表达内涎蛋白,这进一步提示MSC通过分化为肿瘤基质成纤维细胞对肿瘤基质有潜在贡献。