Kubota S, Ito H, Ishibashi Y, Seyama Y
Department of Physiological Chemistry and Nutrition, Faculty of Medicine, The University of Tokyo, Japan.
Int J Cancer. 1997 Jan 6;70(1):106-11. doi: 10.1002/(sici)1097-0215(19970106)70:1<106::aid-ijc16>3.0.co;2-j.
Proteolytic enzymes, such as matrix metalloproteases (MMPs), play a pivotal role in cancer invasion and metastasis. Invasive human rhabdomyosarcoma cells (RD) secreted proMMP-2 (72-kDa progelatinase). We found that anti-alpha3 and -alpha2 integrin antibodies induced the activated form of MMP-2 and enhanced proMMP-2 secretion by RD cells. The effect of anti-alpha2 integrin antibody was less prominent than that seen with anti-alpha3 integrin antibody. Moreover, we have found that anti-alpha3 and -alpha2 integrin antibodies enhanced RD-cell invasion through matrigel (reconstituted basement membrane) by 2.6- and 2.0-fold respectively this process was abrogated by neutralizing antibody to MMP-2. These data suggest that signaling events induced by anti-alpha3 integrin antibody may be involved in RD-cell invasion as a result of modulation of matrix-metalloprotease expression.
蛋白水解酶，如基质金属蛋白酶（MMPs），在癌症侵袭和转移中起关键作用。侵袭性人横纹肌肉瘤细胞（RD）分泌前MMP-2（72 kDa前胶原酶）。我们发现，抗α3和α2整合素抗体诱导MMP-2的活化形式，并增强RD细胞的前MMP-2分泌。抗α2整合素抗体的作用不如抗α3整合素抗体明显。此外，我们发现抗α3和α2整合素抗体分别使RD细胞通过基质胶（重组基底膜）的侵袭增强了2.6倍和2.0倍，此过程被MMP-2中和抗体消除。这些数据表明，抗α3整合素抗体诱导的信号事件可能通过调节基质金属蛋白酶表达参与RD细胞侵袭。
