Danen E H, van Kraats A A, Cornelissen I M, Ruiter D J, van Muijen G N
Department of Pathology, University Hospital St. Radboud, Nijmegen, The Netherlands.
Biochem Biophys Res Commun. 1996 Sep 4;226(1):75-81. doi: 10.1006/bbrc.1996.1313.
Even though integrin alpha v beta 3 is thought to play a role in invasive growth of melanomas, some metastatic melanoma cell lines lack alpha v beta 3, and downmodulation of alpha v beta 3, expression can enhance the invasive capacity of certain melanoma cells. To further investigate this apparent dualistic role of alpha v beta 3, we transfected beta 3 cDNA into the highly metastatic, beta 3-negative human melanoma cell line MV3. MV3 cells adhered to fibronectin but not to fibrinogen or a synthetic RGD peptide, while MV3-beta 3 adhered to all three RGD-containing adhesive ligands, and this adhesion was inhibited by LM609 alpha v beta 3 mAb. Expression of alpha v beta 3 did not affect MV3 in vitro proliferation or in vivo tumorigenicity upon subcutaneous inoculation into nude mice. In contrast, it strongly reduced invasion in matrigel and lung colonization in nude mice of MV3 cells. Thus, certain melanoma cell lines have adopted a metastatic strategy in the absence of alpha v beta 3, and in such cells expression of this integrin leads to a less aggressive phenotype.
尽管整联蛋白αvβ3被认为在黑色素瘤的侵袭性生长中起作用，但一些转移性黑色素瘤细胞系缺乏αvβ3，并且αvβ3表达的下调可增强某些黑色素瘤细胞的侵袭能力。为了进一步研究αvβ3这种明显的双重作用，我们将β3 cDNA转染到高转移性、β3阴性的人黑色素瘤细胞系MV3中。MV3细胞可黏附于纤连蛋白，但不黏附于纤维蛋白原或合成的RGD肽，而MV3-β3可黏附于所有三种含RGD的黏附配体，并且这种黏附被LM609αvβ3单克隆抗体抑制。αvβ3的表达不影响MV3在体外的增殖，也不影响其皮下接种到裸鼠体内后的致瘤性。相反，它强烈降低了MV3细胞在基质胶中的侵袭以及在裸鼠肺部的定植。因此，某些黑色素瘤细胞系在缺乏αvβ3的情况下采取了转移策略，并且在这类细胞中这种整联蛋白的表达导致侵袭性较低的表型。
