Benelli R, Adatia R, Ensoli B, Stetler-Stevenson W G, Santi L, Albini A
Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Oncol Res. 1994;6(6):251-7.
In the initial phases of angiogenesis, endothelial cells must degrade and cross the vessel basement membrane, as do tumor cells during invasion and metastasis formation. Various metalloproteinases have been implicated in tumor cell invasion, in particular MMP-2 (72 kDa collagenase IV, gelatinase A), which has been demonstrated to be associated with tumor metastasis formation. Supernatants from AIDS-Kaposi sarcoma (KS) cells induce normal endothelial cells to invade through a reconstituted basement membrane (Matrigel) in vitro, which correlates with the angiogenic potential of KS cells in vivo. Here we demonstrate that two specific inhibitors of MMP-2, TIMP-2 and a peptide from the MMP-2 propeptide region (peptide 74), inhibit endothelial cell invasion induced by AIDS-KS cell supernatants. Smooth muscle cells were much less sensitive to these inhibitors. These data suggest that MMP-2 activation is a key event in endothelial cell invasion, the initial phase of tumor-associated neoangiogenesis. Inhibition of this enzyme could be an effective treatment for KS and tumor-associated angiogenesis.
在血管生成的初始阶段，内皮细胞必须降解并穿过血管基底膜，肿瘤细胞在侵袭和转移形成过程中也是如此。多种金属蛋白酶与肿瘤细胞侵袭有关，尤其是MMP-2（72 kDa胶原酶IV，明胶酶A），已证明其与肿瘤转移形成相关。艾滋病-卡波西肉瘤（KS）细胞的上清液可诱导正常内皮细胞在体外穿过重组基底膜（基质胶），这与KS细胞在体内的血管生成潜力相关。在此我们证明，MMP-2的两种特异性抑制剂，即组织金属蛋白酶抑制剂-2（TIMP-2）和来自MMP-2前肽区的一种肽（肽74），可抑制艾滋病-KS细胞上清液诱导的内皮细胞侵袭。平滑肌细胞对这些抑制剂的敏感性要低得多。这些数据表明，MMP-2激活是内皮细胞侵袭（肿瘤相关新生血管生成的初始阶段）中的关键事件。抑制这种酶可能是治疗KS和肿瘤相关血管生成的有效方法。
