α1 and α2 integrins mediate invasive activity of mouse mammary carcinoma cells through regulation of stromelysin-1 expression
α1 and α2 integrins mediate invasive activity of mouse mammary carcinoma cells through regulation of stromelysin-1 expression
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DOI：
10.1091/mbc.10.2.271
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发表时间：
1999-02-01
影响因子：
3.3
通讯作者：
Bissell, MJ
中科院分区：
文献类型：
--
作者：
Lochter, A;Navre, M;Bissell, MJ
肿瘤细胞的侵袭依赖于细胞迁移和细胞外基质蛋白的降解。我们研究了不同整合素对小鼠乳腺癌细胞侵袭活性的贡献。针对整合素亚基α 6和β 1的抗体，但不针对α 1和α 2，在二维细胞迁移试验中抑制细胞在重建基底膜上的运动，而针对β 1的抗体，但不针对α 6或α 2，干扰细胞粘附到基底膜成分。针对α 1整合素的阻断抗体仅损害细胞与ni型胶原的粘附。针对α 1、α 2、α 6和β 1整合素亚基的抗体，而不是α 5整合素亚基的抗体，减少了重建基底膜的侵袭。整合素α 1和α 2，这有助于只有轻微的运动和粘附，调节蛋白酶的生产。针对α 1和α 2，但不是α 6和β 1，整合素亚基的抗体抑制基质金属蛋白酶基质溶素-l的转录和蛋白质表达。抗α 1和α 2抗体对肿瘤细胞侵袭的抑制作用可通过加入重组基质溶解素-1逆转。相比之下，基质溶解素-I不能挽救抗α 6抗体抑制的侵袭。我们的数据表明α 1和α 2整合素通过调节基质溶解素-1表达赋予侵袭性行为，而α 6整合素调节细胞运动性。这些结果为整合素在肿瘤细胞侵袭过程中的特异性功能提供了新的见解。
Tumor cell invasion relies on cell migration and extracellular matrix proteolysis. We investigated the contribution of different integrins to the invasive activity of mouse mammary carcinoma cells. Antibodies against integrin subunits alpha 6 and beta 1, but not against alpha 1 and alpha 2, inhibited cell locomotion on a reconstituted basement membrane in two-dimensional cell migration assays, whereas antibodies against beta 1, but not against a6 or alpha 2, interfered with cell adhesion to basement membrane constituents. Blocking antibodies against alpha 1 integrins impaired only cell adhesion to type ni collagen. Antibodies against alpha 1, alpha 2, alpha 6, and beta 1, but not alpha 5, integrin subunits reduced invasion of a reconstituted basement membrane. Integrins alpha 1 and alpha 2, which contributed only marginally to motility and adhesion, regulated proteinase production. Antibodies against alpha 1 and alpha 2, but not alpha 6 and beta 1, integrin subunits inhibited both transcription and protein expression of the matrix metalloproteinase stromelysin-l. Inhibition of tumor cell invasion by antibodies against alpha 1 and alpha 2 was reversed by addition of recombinant stromelysin-l. In contrast, stromelysin-l could not rescue invasion inhibited by anti-alpha 6 antibodies. Our data indicate that alpha 1 and alpha 2 integrins confer invasive behavior by regulating stromelysin-1 expression, whereas alpha 6 integrins regulate cell motility. These results provide new insights into the specific functions of integrins during tumor cell invasion.