Bagley Rebecca G, Rouleau Cecile, Morgenbesser Sharon D, Weber William, Cook Brian P, Shankara Srinivas, Madden Stephen L, Teicher Beverly A
Genzyme Corporation, Framingham, MA 01701-9322, USA.
Microvasc Res. 2006 May;71(3):163-74. doi: 10.1016/j.mvr.2006.03.002. Epub 2006 Apr 19.
Anti-angiogenic strategies have largely focused on endothelial cells and progenitors. However, pericytes are also an important component of vasculature. Perivascular cells from normal tissues have been widely reported, yet have not been extensively studied from human tumors. We have investigated pericytes from tumors of patients with lung cancer, the leader of cancer-related deaths in both men and women. Antibodies and magnetic beads were used to isolate cells from non-small cell lung carcinomas (NSCLC). The morphology of the pericytes was distinct with multiple elongated cytoplasmic extensions. Molecular expression of angiogenic genes was quantified by RT-PCR. Flow cytometric analysis shows that NSCLC pericytes express antigens such NG2 and VEGFR1 and present the ganglioside 3G5. The value of pericytes as models of tumor vasculature was demonstrated in cell-culture-based angiogenesis assays such as tube formation and proliferation. Results show that pericytes from some NSCLC but not all were able to maintain tubes networks on Matrigel. Pericyte function can be influenced by angiogenic growth factors or anti-angiogenic agents. Pericytes displayed invasive action against NSCLC clusters in the absence of other cell types. Perivascular cells contribute to the progression of disease and are an attractive target for anti-angiogenic therapy.
抗血管生成策略主要集中在内皮细胞和祖细胞上。然而，周细胞也是脉管系统的重要组成部分。来自正常组织的血管周围细胞已有广泛报道，但尚未对人类肿瘤中的周细胞进行广泛研究。我们研究了肺癌患者肿瘤中的周细胞，肺癌是男性和女性癌症相关死亡的首要原因。使用抗体和磁珠从非小细胞肺癌（NSCLC）中分离细胞。周细胞的形态独特，有多个细长的细胞质延伸。通过逆转录聚合酶链反应（RT-PCR）对血管生成基因的分子表达进行定量。流式细胞术分析表明，NSCLC周细胞表达诸如NG2和血管内皮生长因子受体1（VEGFR1）等抗原，并呈现神经节苷脂3G5。在基于细胞培养的血管生成试验（如管形成和增殖）中，证明了周细胞作为肿瘤脉管系统模型的价值。结果表明，部分而非所有NSCLC的周细胞能够在基质胶上维持管网络。周细胞功能可受血管生成生长因子或抗血管生成剂影响。在不存在其他细胞类型的情况下，周细胞对NSCLC细胞簇表现出侵袭作用。血管周围细胞促进疾病进展，是抗血管生成治疗的一个有吸引力的靶点。
