CD151 enhances cell motility and metastasis of cancer cells in the presence of focal adhesion kinase

CD151 enhances cell motility and metastasis of cancer cells in the presence of focal adhesion kinase
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DOI:
10.1002/ijc.1605
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发表时间:
2002-01-20
影响因子:
6.4
通讯作者:
Fujita, S
Fujita, S
中科院分区:
医学1区
文献类型:
--
作者:
Kohno, M;Hasegawa, H;Fujita, S

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我们已经研究了蛋白质CD 151在细胞运动,侵袭和转移的癌细胞通过使用CD 151-过表达的细胞制备的转染CD 151 cDNA到三个癌细胞系建立从不同的起源,人结肠癌RPM 14788,人胶质母细胞瘤A 172和人纤维肉瘤HT 1080。与对照亲本细胞相比,所有3种CD 151过表达癌细胞对基质胶的侵袭和细胞运动性显著增强。2个转移性CD 151过表达癌细胞系RPM 14788/CD 151和HT 1080/CD 151的肺转移高于对照亲本细胞,并且被抗CD 151单克隆抗体(MAb)SFA 1.2B4显著抑制。为了检测粘着斑激酶(FAK)是否与通过CD 151促进细胞运动和癌细胞侵袭有关,我们将人CD 151 cDNA转染FAK(+/+)或FAK(-/-)成纤维细胞,所述成纤维细胞从FAK缺陷小鼠的胚胎中分离,并比较每个CD 151转染细胞和对照之间对基质胶的侵袭和细胞运动。CD 151转染的FAK(+/+)成纤维细胞对Matrigel的侵袭能力和细胞运动能力明显高于亲本细胞,并被抗CD 151单抗抑制,而CD 151转染的FAK(-/-)成纤维细胞对Matrigel的侵袭能力和细胞运动能力没有明显增强,也不被抗CD 151单抗阻断。这些发现表明CD 151分子增强癌细胞的细胞运动性、侵袭和转移,并且FAK通过CD 151对于这些事件是必需的。(C)2002 Wiley-Liss,Inc.
We have examined the role of the protein CD151 in cell motility, invasion and metastasis of cancer cells by using CD151-overexpressing cells prepared by transfection of CD151 cDNA into three cancer cell lines established from different origins; a human colon cancer RPM14788, a human glioblastoma A 172 and a human fibrosarcoma HT 1080. Invasion into Matrigel and cell motility of all 3 CD151-overexpressing cancer cells were enhanced significantly when compared to control parental cells. Pulmonary metastasis of 2 metastatic CD151-overexpressing cancer cell lines, RPM14788/CD151 and HT1080/CD151, was higher than that of control parental cells and was markedly inhibited by anti-CD151 monoclonal antibody (MAb), SFA1.2B4. To examine whether focal adhesion kinase (FAK) is associated with promotion of cell motility and invasion of cancer cells through CD151, we transfected human CD151 cDNA into FAK (+/+) or FAK (-/-) fibroblasts that were isolated from embryos in FAK-deficient mice and compared invasion into Matrigel and cell motility between each CD151-transfected cells and controls. The invasion into Matrigel and cell motility of CD151 transfected FAK (+/+) fibroblasts increased significantly above those of parental cells and were inhibited by anti-CD151 MAb, whereas those of CD151-transfected FAK (-/-) fibroblasts were not enhanced at all and were not blocked by anti-CD151 MAb. These findings indicate that the CD151 molecule enhances cell motility, invasion and metastasis of cancer cells and that FAK is needed for these events through CD151. (C) 2002 Wiley-Liss, Inc.