Walter-Yohrling Jennifer, Pratt Bruce M, Ledbetter Steve, Teicher Beverly A
Department of Tumor Biology, Genzyme Molecular Oncology, Genzyme Corporation, Five Mountain Road, Framingham, MA 01701, USA.
Cancer Chemother Pharmacol. 2003 Oct;52(4):263-9. doi: 10.1007/s00280-003-0664-2. Epub 2003 Jul 17.
In an effort to study the importance of stromal involvement in angiogenesis, we developed a novel, multicellular model that utilizes three of the primary cell types involved in tumor angiogenesis.
Fluorescently labeled human microvascular endothelial cells (HMVECs), 10T1/2 cells and myofibroblasts were incubated in the presence of a three-dimensional tumor cell cluster resuspended in collagen and embedded in Matrigel.
HMVECs cultured in the presence of a human SKOV-3 ovarian carcinoma tumor cell cluster, surrounded the tumor cell cluster, while myofibroblasts invaded the cluster, localizing within the tumor cell mass. In contrast, 10T1/2 cells, a pluripotent mouse mesenchymal cell line with pericyte-like properties, did not demonstrate the same invasive phenotype. HMVECs cultured in the presence of myofibroblasts invaded the tumor cell cluster and colocalized with the myofibroblasts as demonstrated by fluorescent microscopy and immunohistochemistry. The angiogenesis inhibitors SU6668 and paclitaxel inhibited stromal invasion, while a broad-spectrum matrix metalloproteinase inhibitor did not.
This model emphasizes the critical interaction between endothelial cells and myofibroblasts and provides a more complete in vitro model for studying angiogenesis and tumor progression.
为了研究基质参与血管生成的重要性，我们开发了一种新型的多细胞模型，该模型利用了肿瘤血管生成中涉及的三种主要细胞类型。
将荧光标记的人微血管内皮细胞（HMVECs）、10T1/2细胞和成肌纤维细胞与悬浮在胶原蛋白中并包埋在基质胶中的三维肿瘤细胞簇一起孵育。
在人SKOV-3卵巢癌细胞簇存在的情况下培养的HMVECs围绕肿瘤细胞簇，而成肌纤维细胞侵入该簇，定位在肿瘤细胞团块内。相比之下，10T1/2细胞是一种具有周细胞样特性的多能小鼠间充质细胞系，未表现出相同的侵袭表型。在成肌纤维细胞存在的情况下培养的HMVECs侵入肿瘤细胞簇，并与成肌纤维细胞共定位，荧光显微镜和免疫组织化学结果表明了这一点。血管生成抑制剂SU6668和紫杉醇抑制基质侵袭，而广谱基质金属蛋白酶抑制剂则无此作用。
该模型强调了内皮细胞和成肌纤维细胞之间的关键相互作用，并为研究血管生成和肿瘤进展提供了一个更完整的体外模型。
