Integrin beta 3 cDNA transfection into a highly metastatic alpha v beta 3-negative human melanoma cell line inhibits invasion and experimental metastasis

Integrin beta 3 cDNA transfection into a highly metastatic alpha v beta 3-negative human melanoma cell line inhibits invasion and experimental metastasis
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DOI:
10.1006/bbrc.1996.1313
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发表时间:
1996-09-04
影响因子:
3.1
通讯作者:
vanMuijen, GNP
vanMuijen, GNP
中科院分区:
生物学4区
文献类型:
--
作者:
Danen, EHJ;vanKraats, AA;vanMuijen, GNP

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尽管整合素α v β 3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α v β 3,并且α v β 3表达的下调可以增强某些黑色素瘤细胞的侵袭能力。为了进一步研究α v β 3的这种明显的双重作用,我们将β 3 cDNA转染到高转移性β 3阴性人黑色素瘤细胞系MV 3中。MV 3细胞粘附于纤连蛋白,但不粘附于纤维蛋白原或合成的RGD肽,而MV 3-β 3粘附于所有三种含RGD的粘附配体,并且这种粘附被LM 609 α v β 3 mAb抑制。α v β 3的表达不影响MV 3在体外增殖或皮下接种到裸鼠后的体内致瘤性。相反,它强烈降低MV 3细胞在基质胶中的侵袭和在裸鼠中的肺定殖。因此,某些黑色素瘤细胞系在缺乏α v β 3的情况下采用了转移策略,并且在这样的细胞中,这种整联蛋白的表达导致侵袭性较低的表型。(C)出版社:Academic Press,Inc.
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. (C) 1996 Academic Press, Inc.