Role for beta3 integrins in human melanoma growth and survival.
Role for beta3 integrins in human melanoma growth and survival.
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发表时间：
2002
影响因子：
6.4
通讯作者：
M. Trikha;J. Tímár;A. Zacharek;J. Nemeth;Yinlong Cai;B. Dome;B. Somlai;E. Raso;A. Ladányi;K. Honn
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作者：
M. Trikha;J. Tímár;A. Zacharek;J. Nemeth;Yinlong Cai;B. Dome;B. Somlai;E. Raso;A. Ladányi;K. Honn
αIIbbeta3 整合素在调节血小板功能中的作用已得到充分认识，但其在肿瘤进展和转移中的作用却尚未得到充分认识。我们研究的目的是确定人实体瘤细胞中 αIIbbeta3 整合素表达的功能相关性。一项对人类黑色素瘤活检 (n = 24) 的研究表明，αIIbbeta3 表达随着肿瘤厚度的增加而增加，这表明有转移倾向。在厚度范围为 0-1.5 mm、1.5-4.0 mm 和 >4 mm 的黑色素瘤中，αIIbbeta3 的表达分别为 8% (+/-1.8)、33% (+/-10.4) 和 62% (+/-5)； alphavbeta3 在所有类别中都同样高。为了确定生物学功能，我们将 alphaIIbbeta3 稳定转染到表达 alphavbeta3 但不表达 alphaIIbbeta3 的人黑色素瘤细胞中。 alphavbeta3 的表面表达在 alphaIIbbeta3 (+) 和模拟转染的对应物之间保持不变。 αIIbbeta3 (+) 细胞在纤维蛋白原上粘附、扩散和迁移的能力增强。它们在玻连蛋白上的附着、传播和迁移能力下降。免疫细胞化学显示αIIbbeta3的表达取代了焦点接触点的αvbeta3。当皮下植入 SCID 小鼠时，与模拟细胞相比，αIIbbeta3 (+) 细胞形成约 4 倍大的肿瘤，并且肿瘤内的细胞凋亡水平降低。结果表明，人黑色素瘤细胞中 2β3 整合素 alphavbeta3 和 alphaIIbbeta3 的共表达可增强细胞存活并促进体内生长。
The role of alphaIIbbeta3 integrin in regulating platelet function is well appreciated, whereas its role in tumor progression and metastasis is not. The purpose of our study was to determine a functional relevance to expression of alphaIIbbeta3 integrin in cells derived from human solid tumors. A study of human melanoma biopsies (n = 24) showed that alphaIIbbeta3 expression increased with tumor thickness, which is indicative of metastatic propensity. Expression of alphaIIbbeta3 was 8% (+/-1.8), 33% (+/-10.4) and 62% (+/-5) in melanomas ranging in thickness from 0-1.5 mm, 1.5-4.0 mm and >4 mm, respectively; alphavbeta3 was equally high all categories. To determine biological function, we stably transfected alphaIIbbeta3 into human melanoma cells that express alphavbeta3, but not alphaIIbbeta3. Surface expression of alphavbeta3 remained unaltered between alphaIIbbeta3 (+) and mock transfected counterparts. The alphaIIbbeta3 (+) cells possessed increased ability to adhere, spread and migrate on fibrinogen. They had decreased ability to attach, spread and migrate on vitronectin. Immunocytochemistry showed that expression of alphaIIbbeta3 displaced alphavbeta3 from focal contact points. When implanted subcutaneously into SCID mice, the alphaIIbbeta3 (+) cells developed approximately 4-fold larger tumors when compared to their mock counterparts and the level of apoptosis was reduced within the tumors. Results suggest that co-expression of the 2 beta3 integrins, alphavbeta3 and alphaIIbbeta3, in human melanoma cells enhanced cell survival and promoted growth in vivo.