Graeven U, Herlyn M
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
J Immunother (1991). 1992 Oct;12(3):199-202. doi: 10.1097/00002371-199210000-00012.
Based on the clinicopathological classification of distinct stages of tumor progression in the melanocytic system, we have investigated the in vitro growth patterns and requirements of normal melanocytes and melanocytes isolated from different lesions of melanoma progression. Normal melanocytes depend on a combination of insulin-like growth factor (IGF-I) or insulin, 12-O-tetradecanoyl phorbol-13-acetate (TPA), alpha-melanocyte stimulating hormone (alpha-MSH), and basic fibroblast growth factor (bFGF) for in vitro proliferation. Nevus cells display a reduced need for TPA and are largely independent of bFGF. Both melanocytes and nevus cells have a finite lifespan in vitro and show no spontaneous transformation, whereas melanoma cells can be grown indefinitely in vitro. Cells from primary melanomas require only IGF-I or insulin for continuous growth, and metastatic melanoma cells can proliferate in base medium without addition of any growth factors or proteins. This progressive growth autonomy is paralleled by an increased competence for endogenous growth factor production. Among these growth factors, bFGF and melanoma growth-stimulatory activity (MGSA) act in an autocrine fashion. Melanoma-derived growth factors without apparent autocrine function, such as platelet-derived growth factor A and B (PDGF-A and PDGF-B) and transforming growth factor-alpha (TGF-alpha), might still be important for melanoma growth by stimulating surrounding normal fibroblasts, endothelial cells, or keratinocytes to secrete growth-promoting factors. The significance of growth factors such as transforming growth factor-beta (TGF-beta) and melanoma-inhibiting activity II (MIA II), which have a potentially negative autocrine function, remains unknown. The successful propagation of melanocytic cells of all stages of melanoma progression has yielded valuable insight into the mechanisms of growth regulation and malignant transformation.
基于黑素细胞系统肿瘤进展不同阶段的临床病理分类，我们研究了正常黑素细胞以及从黑色素瘤进展不同病变中分离出的黑素细胞的体外生长模式和需求。正常黑素细胞在体外增殖依赖于胰岛素样生长因子（IGF-I）或胰岛素、12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）、α - 黑素细胞刺激素（α - MSH）和碱性成纤维细胞生长因子（bFGF）的组合。痣细胞对TPA的需求减少，并且在很大程度上不依赖于bFGF。黑素细胞和痣细胞在体外都有有限的寿命，且未显示出自发转化，而黑色素瘤细胞在体外可以无限增殖。原发性黑色素瘤细胞仅需要IGF-I或胰岛素就能持续生长，转移性黑色素瘤细胞可以在不添加任何生长因子或蛋白质的基础培养基中增殖。这种逐渐增加的生长自主性与内源性生长因子产生能力的增强相平行。在这些生长因子中，bFGF和黑色素瘤生长刺激活性（MGSA）以自分泌方式起作用。没有明显自分泌功能的黑色素瘤衍生生长因子，如血小板衍生生长因子A和B（PDGF - A和PDGF - B）以及转化生长因子-α（TGF - α），可能通过刺激周围正常成纤维细胞、内皮细胞或角质形成细胞分泌促生长因子，对黑色素瘤生长仍然很重要。具有潜在负自分泌功能的生长因子，如转化生长因子-β（TGF - β）和黑色素瘤抑制活性II（MIA II）的意义仍然未知。黑色素瘤进展各阶段黑素细胞的成功培养，为生长调节和恶性转化机制提供了有价值的见解。
