Natali P G, Nicotra M R, Di Filippo F, Bigotti A
Regina Elena Cancer Institute, Rome, Italy.
Br J Cancer. 1995 Jun;71(6):1243-7. doi: 10.1038/bjc.1995.240.
In vitro studies have demonstrated that fibronectin (FN) can deliver a mitogenic signal to quiescent human melanoma cells and that the alpha 5/beta 1-integrin receptor mediates this stimulus. In view of this finding we have analysed the in vivo expression of FN, and of ED-A and ED-B FN isoforms, in benign and malignant lesions of melanocyte origin. In the same specimens the expression of fibronectin integrin receptors was evaluated. The results demonstrate that, while detection of FN does not correlate with transformation and tumour progression, the expression of the two isoforms is associated with transformation and that only the ED-A variant is found in metastases. Integrin phenotyping disclosed that alpha 3/beta 1 expression is associated with tumour progression, alpha v/beta 3 is a marker of transformation, alpha 4 is rarely expressed and alpha 5 is expressed by about 50% and 30% of the primary and metastatic lesions respectively. Taken together, the results of this study demonstrate that transformation and tumour progression of the melanocyte lineage are associated with modulation of expression of FN isoforms and FN integrin receptors. Furthermore, the expression of alpha 5-integrin in a considerable percentage of primary and metastatic lesions indicates that FN may deliver a proliferative stimulus to melanoma cells in vivo.
体外研究表明，纤连蛋白（FN）可向静止的人黑素瘤细胞传递促有丝分裂信号，且α5/β1整合素受体介导这种刺激。鉴于这一发现，我们分析了黑素细胞来源的良性和恶性病变中FN以及ED - A和ED - B FN亚型的体内表达情况。在相同的标本中评估了纤连蛋白整合素受体的表达。结果表明，虽然FN的检测与细胞转化和肿瘤进展无关，但两种亚型的表达与细胞转化相关，且仅在转移灶中发现ED - A变体。整合素表型分析显示，α3/β1的表达与肿瘤进展相关，αv/β3是细胞转化的标志物，α4很少表达，α5分别在约50%的原发性病变和30%的转移病变中表达。综上所述，本研究结果表明黑素细胞谱系的细胞转化和肿瘤进展与FN亚型及FN整合素受体表达的调节有关。此外，相当比例的原发性和转移病变中α5整合素的表达表明FN可能在体内向黑素瘤细胞传递增殖刺激。
