Adenoviral gene transfer of β3 integrin subunit induces conversion from radial to vertical growth phase in primary human melanoma
Adenoviral gene transfer of β3 integrin subunit induces conversion from radial to vertical growth phase in primary human melanoma
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DOI：
10.1016/s0002-9440(10)65730-6
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发表时间：
1998-11-01
影响因子：
6
通讯作者：
Herlyn, M
中科院分区：
文献类型：
--
作者：
Hsu, MY;Shih, DT;Herlyn, M
α v β 3玻璃体连接蛋白受体β 3亚基在黑色素瘤细胞上的表达与肿瘤厚度、侵袭和转移能力有关。为了研究α v β 3在原发性黑色素瘤从非致瘤性径向生长到致瘤性垂直生长的复杂过程中的作用，我们使用腺病毒载体进行基因转移，研究了在早期黑色素瘤细胞中过表达α v β 3的生物学后果。在放射生长期原发性黑色素瘤细胞中，功能性α v β 3的过表达1)促进锚定依赖性和非依赖性生长，2)在三维皮肤重建中启动从表皮到真皮层的侵袭性生长，3)阻止入侵细胞的凋亡，4)增加肿瘤在体内的生长。因此，α v β 3在原发性黑色素瘤从非致瘤性放射状生长阶段到致瘤性侵袭性垂直生长阶段的发展过程中具有多种生物学功能。
Expression of the beta 3 subunit of the alpha v beta 3 vitronectin receptor on melanoma cells is associated with tumor thickness and the ability to invade and metastasize. To address the role of alpha v beta 3 in the complex process of progression from the nontumorigenic radial to the tumorigenic vertical growth phase of primary melanoma, we examined the biological consequences of overexpressing alpha v beta 3 in early-stage melanoma cells using an adenoviral vector for gene transfer. Overexpression of functional alpha v beta 3 in radial growth phase primary melanoma cells 1) promotes both anchorage-dependent and -independent growth, 2) initiates invasive growth from the epidermis into the dermis in three-dimensional skin reconstructs, 3) prevents apoptosis of invading cells, and 4) increases tumor growth in vivo. Thus, alpha v beta 3 serves diverse biological functions during the progression from the nontumorigenic radial growth phase to the tumorigenic and invasive vertical growth phase primary melanoma.