Autocrine and paracrine roles for growth factors in melanoma.
Autocrine and paracrine roles for growth factors in melanoma.
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作者：
I. Shih;M. Herlyn
在人类黑素细胞系统中，不同的生物学和组织病理学特征表征了肿瘤向更具侵袭性表型进展的每个阶段。伴随黑色素瘤进展的一个最重要的方面是肿瘤细胞获得生长自主性和多种生长因子和受体的表达，而不是正常的黑色素细胞。在黑色素瘤细胞产生的生长因子中，bFGF、tgf - α、tgf - β、PDGF A链和B链、MGSA和白介素已被广泛表征。这些黑色素瘤衍生因子介导的复杂信号网络负责黑色素瘤细胞的自分泌生长刺激和生长因子的旁分泌作用，以产生有利于肿瘤生存和侵袭的微环境。bFGF是黑色素瘤细胞自分泌刺激的最佳表征候选者。此外，bFGF和其他未明显参与自分泌环的生长因子已被证明可以激活邻近的基质细胞，参与血管生成、纤维基质形成、激活正常细胞产生的蛋白水解酶、促进肿瘤细胞与细胞外基质和内皮的粘附相互作用以及抑制局部免疫。需要能够解释正常细胞和肿瘤细胞之间复杂相互作用的实验模型，以进一步探索生长因子及其受体的自分泌和旁分泌作用在黑色素瘤发生和进展中的作用。
Distinct biologic and histopathological features characterizing each stage of tumor progression toward a more aggressive phenotype have been defined in the human melanocytic cell system. One of the most significant aspects accompanying melanoma progression is the acquisition of growth autonomy and the expression of multiple growth factors and receptors by tumor cells but not by normal melanocytes. Among the growth factors produced by melanoma cells, bFGF, TGF-alpha, TGF-beta, PDGF A and B chains, MGSA, and interleukins have been extensively characterized. The complex signaling networks mediated by these melanoma-derived factors are responsible for the autocrine growth stimulation of melanoma cells and for paracrine actions of growth factors in the generation of a microenvironment favorable for tumor survival and invasion. bFGF is the best characterized candidate for autocrine stimulation in melanoma cells. In addition, bFGF and other growth factors not apparently involved in autocrine loops have been shown to activate neighboring stromal cells and to participate in angiogenesis, fibrous stroma formation, activation of proteolytic enzymes produced by normal cells, promotion of adhesive interactions between tumor cells and extracellular matrix and endothelium, and suppression of local immunity. Experimental models that can account for the complex interactions between normal and tumor cells are needed to further explore the roles of autocrine and paracrine actions of growth factors and their receptors in melanoma development and progression.