Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
Anticancer Res. 2014 Dec;34(12):7091-6.
Cluster of differentiation 147 (CD147)/basigin on the malignant tumor cell surface is critical for tumor proliferation, invasiveness, metastasis, and angiogenesis. CD147 expressed on malignant melanoma cells can induce tumor cell invasion by stimulating the production of matrix metalloproteinases (MMPs) by surrounding fibroblasts. Membrane vesicles, microvesicles and exosomes have attracted attention, as vehicles of functional molecules and their association with CD147 has been reported. Cleaved CD147 fragments released from tumor cells were reported to interact with fibroblasts. We investigated the intercellular mechanisms by which CD147 stimulates fibroblasts to induce MMP2 activity.
CD147 was knocked-down using short hairpin RNA (shRNA). The stimulatory effect of CD147 in cell culture supernatants, microvesicles, and exosomes on the enzymatic activity of MMP2 was examined by gelatin zymography.
Supernatants from A375 control cells induced increased enzymatic activity of fibroblasts; such activity was significantly lower in CD147 knock-down cells.
Cleaved CD147 plays a pivotal role in stimulating fibroblasts to induce MMP2 activity.
肿瘤细胞表面的分化簇 147（CD147）/basigin 对肿瘤的增殖、侵袭、转移和血管生成至关重要。恶性黑色素瘤细胞表面表达的 CD147 可以通过刺激周围成纤维细胞产生基质金属蛋白酶（MMPs）来诱导肿瘤细胞侵袭。膜囊泡、微泡和外泌体引起了人们的关注，因为它们是功能分子的载体，并且已经报道了它们与 CD147 的关联。据报道，从肿瘤细胞释放的裂解的 CD147 片段与成纤维细胞相互作用。我们研究了 CD147 刺激成纤维细胞诱导 MMP2 活性的细胞间机制。
使用短发夹 RNA（shRNA）敲低 CD147。通过明胶酶谱法检测细胞培养上清液、微泡和外泌体中 CD147 对 MMP2 酶活性的刺激作用。
对照细胞 A375 的上清液诱导成纤维细胞的酶活性增加；在 CD147 敲低细胞中，这种活性显著降低。
裂解的 CD147 在外泌体中在刺激成纤维细胞诱导 MMP2 活性方面起着关键作用。
