Pericytes and endothelial precursor cells: Cellular interactions and contributions to malignancy
Pericytes and endothelial precursor cells: Cellular interactions and contributions to malignancy
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DOI：
10.1158/0008-5472.can-04-4337
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发表时间：
2005-11-01
期刊：
影响因子：
11.2
通讯作者：
Teicher, BA
中科院分区：
文献类型：
--
作者：
Bagley, RG;Weber, W;Teicher, BA
肿瘤血管是不规则的、异常的，并且是肿瘤生长所必需的。周细胞和内皮前体细胞（EPC）在血管生成条件下有助于血管的形成。作为培养物中的原代细胞，周细胞和EPC共享许多特性，例如管/网络形成和对血管生成途径的选择性激酶抑制剂的反应。细胞表面蛋白的表达，包括血小板衍生的生长因子受体，血管细胞粘附分子，细胞间粘附分子，CD 105，结蛋白，神经生长蛋白聚糖2是相似的周细胞和EPC之间，而P1 H12和淋巴细胞功能相关抗原-1的表达明显区分的细胞类型。在血管生成基因表达的分子谱中观察到进一步的区别。在共培养实验系统中，周细胞或EPC增强了MDA-MB-231乳腺癌细胞的侵袭。南卡罗来纳与共注射辐照的周细胞或EPC相比，共注射活的周细胞或EPC沿着MDA-MB-231细胞导致肿瘤生长速率增加。微血管密度分析表明，在MDA-MB-231肿瘤中，有或没有EPC或周细胞没有差异。然而，血管的免疫组织化学染色表明，EPC和周细胞可能稳定或正常化的血管，而不是启动血管发生。此外，由EPC和癌细胞共注射引起的肿瘤更容易发展淋巴管。这些结果支持这样的观点，即周细胞和EPC有助于恶性肿瘤，并且这些细胞类型可以用作肿瘤血管发育的基于细胞的模型和可以提供治疗益处的药剂的选择。
Tumor vasculature is irregular, abnormal, and essential for tumor growth. Pericytes and endothelial precursor cells (EPC) contribute to the formation of blood vessels under angiogenic conditions. As primary cells in culture, pericytes and EPC share many properties such as tube/network formation and response to kinase inhibitors selective for angiogenic pathways. Expression of cell surface proteins including platelet-derived growth factor receptor, vascular cell adhesion molecule, intercellular adhesion molecule, CD105, desmin, and neural growth proteoglycan 2 was similar between pericytes and EPC, whereas expression of P1H12 and lymphocyte function-associated antigen-1 clearly differentiates the cell types. Further distinction was observed in the molecular profiles for expression of angiogenic genes. Pericytes or EPC enhanced the invasion of MDA-MB-231 breast cancer cells in a coculture assay system. The s.c. coinjection of live pericytes or EPC along with MDA-MB-231 cells resulted in an increased rate of tumor growth compared with coinjection of irradiated pericytes or EPC. Microvessel density analysis indicated there was no difference in MDA-MB-231 tumors with or without EPC or pericytes. However, immunohistochemical staining of vasculature suggested that EPC and pericytes may stabilize or normalize vasculature rather than initiate vasculogenesis. In addition, tumors arising from the coinjection of EPC and cancer cells were more likely to develop lymphatic vessels. These results support the notion that pericytes and EPC contribute to malignancy and that these cell types can be useful as cell-based models for tumor vascular development and selection of agents that may provide therapeutic benefit.