Authors' Affiliations: Department of Restorative Sciences, Angiogenesis Research Laboratory, University of Michigan School of Dentistry; Department of Biomedical Engineering, University of Michigan College of Engineering; Department of Otolaryngology, University of Michigan School of Medicine, Ann Arbor, Michigan; and Department of Oral Pathology, School of Dentistry, Universidade Federal do Rio Grande do Sul; Porto Alegre, Rio Grande do Sul, Brazil.
Authors' Affiliations: Department of Restorative Sciences, Angiogenesis Research Laboratory, University of Michigan School of Dentistry; Department of Biomedical Engineering, University of Michigan College of Engineering; Department of Otolaryngology, University of Michigan School of Medicine, Ann Arbor, Michigan; and Department of Oral Pathology, School of Dentistry, Universidade Federal do Rio Grande do Sul; Porto Alegre, Rio Grande do Sul, BrazilAuthors' Affiliations: Department of Restorative Sciences, Angiogenesis Research Laboratory, University of Michigan School of Dentistry; Department of Biomedical Engineering, University of Michigan College of Engineering; Department of Otolaryngology, University of Michigan School of Medicine, Ann Arbor, Michigan; and Department of Oral Pathology, School of Dentistry, Universidade Federal do Rio Grande do Sul; Porto Alegre, Rio Grande do Sul, BrazilAuthors' Affiliations: Department of Restorative Sciences, Angiogenesis Research Laboratory, University of Michigan School of Dentistry; Department of Biomedical Engineering, University of Michigan College of Engineering; Department of Otolaryngology, University of Michigan School of Medicine, Ann Arbor, Michigan; and Department of Oral Pathology, School of Dentistry, Universidade Federal do Rio Grande do Sul; Porto Alegre, Rio Grande do Sul, Brazil
Cancer Res. 2014 May 15;74(10):2869-81. doi: 10.1158/0008-5472.CAN-13-2032. Epub 2014 Mar 31.
Emerging evidence suggests that endothelial cell-secreted factors contribute to the pathobiology of squamous cell carcinoma (SCC) by enhancing invasive migration and resistance to anoikis. Here, we report that SCC cells within the perivascular niche have undergone epithelial to mesenchymal transition (EMT) in a primary human SCC of a patient that developed distant metastases. Endothelial cell-secreted EGF induced EMT of human SCC cells in vitro and also induced acquisition of a stem-like phenotype. In vivo, tumor xenografts vascularized with EGF-silenced endothelial cells exhibited a smaller fraction of cancer stem-like cells (ALDH(+)CD44(+)) and were less invasive than tumors vascularized with control endothelial cells. Collectively, these results demonstrated that endothelial cell-EGF induces EMT and acquisition of stem-like properties by head and neck tumor cells. On this basis, we suggest that vascular endothelial cells contribute to tumor dissemination by secreting factors that endow carcinoma cells with enhanced motility and stemness.
新出现的证据表明，内皮细胞分泌的因子通过增强侵袭性迁移和抗失巢凋亡，促进鳞状细胞癌 (SCC) 的病理生物学。在这里，我们报告在一名发生远处转移的患者的原发性人 SCC 中，血管周围巢内的 SCC 细胞已经经历上皮间质转化 (EMT)。内皮细胞分泌的 EGF 在体外诱导人 SCC 细胞发生 EMT，并且还诱导获得干细胞样表型。在体内，用沉默 EGF 的内皮细胞血管化的肿瘤异种移植物中，具有癌症干细胞样细胞（ALDH(+)CD44(+)）的比例较小，并且比用对照内皮细胞血管化的肿瘤侵袭性更小。总的来说，这些结果表明内皮细胞-EGF 通过诱导头颈部肿瘤细胞发生 EMT 和获得干细胞样特性。在此基础上，我们认为血管内皮细胞通过分泌赋予癌细胞增强的迁移能力和干细胞特性的因子，促进肿瘤的扩散。
