Kanekura Takuro, Chen Xiang, Kanzaki Tamotsu
Department of Dermatology, Kagoshima University Faculty of Medicine, 8-35-1 Sakuragaoka, Kagoshima 890-8530, Japan.
Int J Cancer. 2002 Jun 1;99(4):520-8. doi: 10.1002/ijc.10390.
EMMPRIN, which is identical to human basigin (CD147), interacts with fibroblasts and stimulates expression of MMPs, which play an important role in tumor invasiveness and metastasis. In the present study, we demonstrated that coculture of basigin-expressing human MM cells with dermal fibroblasts resulted in the induction of MMP-1, MMP-2, MMP-3 and MT1-MMP production by fibroblasts and of melanoma cell invasion through a reconstituted basement membrane. Antibody to basigin inhibited both the production of MMPs by fibroblasts and the invasiveness of melanoma cells. Expression of basigin and MMPs in MM and surrounding fibroblasts was examined immunohistochemically in 28 specimens from 18 MM patients without metastasis and 10 with metastasis, to investigate whether basigin plays a role in metastasis of MM in vivo. Basigin was expressed in melanoma cells but not in fibroblasts. MM with metastasis had significantly higher basigin expression compared to MM without metastasis. There were significant differences between MMs with and without metastasis in the expression of MMPs in both melanoma cells and fibroblasts. Expression of MMPs in fibroblasts was positively correlated with expression levels of basigin. These immunohistochemic findings indicate that MMPs might be expressed in fibroblasts as well as melanoma cells concomitantly with basigin, which was expressed in melanoma cells more frequently in MM with metastasis. Basigin is highly expressed in melanoma cells and may play an important role in their invasiveness and metastasis by stimulating surrounding fibroblasts to express MMPs.
细胞外基质金属蛋白酶诱导因子（EMMPRIN）与人基底膜蛋白（CD147）相同，它与成纤维细胞相互作用并刺激基质金属蛋白酶（MMPs）的表达，而MMPs在肿瘤侵袭和转移中起重要作用。在本研究中，我们证明将表达基底膜蛋白的人骨髓瘤细胞与真皮成纤维细胞共培养，可诱导成纤维细胞产生MMP-1、MMP-2、MMP-3和MT1-MMP，并使黑色素瘤细胞通过重组基底膜发生侵袭。抗基底膜蛋白抗体可抑制成纤维细胞产生MMPs以及黑色素瘤细胞的侵袭性。对18例无转移和10例有转移的骨髓瘤患者的28份标本进行免疫组织化学检查，以研究基底膜蛋白在骨髓瘤体内转移中是否起作用。基底膜蛋白在黑色素瘤细胞中表达，但在成纤维细胞中不表达。有转移的骨髓瘤与无转移的骨髓瘤相比，基底膜蛋白表达显著更高。有转移和无转移的骨髓瘤在黑色素瘤细胞和成纤维细胞中MMPs的表达上存在显著差异。成纤维细胞中MMPs的表达与基底膜蛋白的表达水平呈正相关。这些免疫组织化学结果表明，MMPs可能与基底膜蛋白同时在成纤维细胞和黑色素瘤细胞中表达，而基底膜蛋白在有转移的骨髓瘤中更频繁地在黑色素瘤细胞中表达。基底膜蛋白在黑色素瘤细胞中高表达，可能通过刺激周围成纤维细胞表达MMPs在其侵袭和转移中起重要作用。
