Tumor cell populations differ in angiogenic activity: a model system for spontaneous angiogenic switch can tell us why.
Tumor cell populations differ in angiogenic activity: a model system for spontaneous angiogenic switch can tell us why.
复制标题
肿瘤细胞群的血管生成活性不同：自发血管生成转换的模型系统可以告诉我们原因。
DOI：
10.1093/jnci/djj099
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Tosato,Giovanna
中科院分区：
文献类型：
--
作者：
Narazaki,Masashi;Tosato,Giovanna
Masashi Narazaki, Giovanna Tosato growing tumors “angiogenic” because they appeared red and were vascularized, as opposed to the dormant cancers, which they termed “nonangiogenic” because they appeared white and poorly vascularized. Cells derived from the angiogenic tumors were reinjected into SCID mice. This time, the tumors grew much more rapidly in the mice and became palpable by 21 days after injection. Thus, by using this method, the authors had selected from three established cell lines subpopulations of tumor cells with markedly different characteristics with respect to tumor formation in mice—that is cells forming indolent tumors, at least indolent for quite some time, or cells forming rapidly growing tumors. The authors looked for differences that could explain these divergent phenotypes. Both cell types had similar proliferation rates in vitro, but compared with nonangiogenic tumors, angiogenic tumors produced substantially greater amounts of the proangiogenic factor basic fibroblast growth factor (bFGF, also referred to as fibroblast growth factor 2, or FGF2) and substantially lower levels of the antiangiogenic factor thrombospondin 1. Levels of VEGF were similarly elevated in nonangiogenic and angiogenic breast carcinoma and glioblastoma cell lines, but angiogenic osteosarcoma cells produced substantially more VEGF than nonangiogenic osteosarcoma cells. Thus, in these examples, the ability of tumor cells to generate indolent or rapidly growing tumors correlated directly with levels of secreted proangiogenic bFGF and indirectly with levels of antiangiogenic t hrombospondin 1. Many activator and inhibitor proteins orchestrate angiogenesis. In addition to the FGF and VEGF protein families, other proangiogenic factors include platelet-derived growth factors, angiopoietins, placental-like growth factor, hepatocyte growth factor, transforming growth factors, stromal-derived factor 1, interleukin 8, and monocyte chemoattractant protein 1 (11). In addition to thrombospondin 1, negative regulators of angio genesis include the Notch ligands Delta4 and Jagged1 (12, 13), vasohibin (14), endostatin (15), angiostatin (16), vasostatin (17), and tumstatin (18). Blood vessels in different tissues may differ phenotypically (19), and at least one tissue-specific proangiogenic factor has been identified (20), suggesting the possibility of tissue-specific regulation of angiogenesis, including the angiogenic switch. Recent studies have explored the possible role in angiogenesis of axon guidance receptors and their ligands, including semaphorins and plexin receptors, Slits and Robo receptors, ephrins and Eph receptors, and netrins-DCC/neogenin and Unc5 receptors (21–23). In some cases, the same factors that provide axons with attractive and repulsive cues have been found to regulate migration and
