Voigt Heike, Houben Roland, Schrama David, Hofmann Uta B, Vetter-Kauczok Claudia S, Becker Jürgen C
Department of Dermatology, Julius Maximilians University, Würzburg, Germany.
Tumour Biol. 2007;28(4):229-37. doi: 10.1159/000107418. Epub 2007 Aug 20.
It was conclusively demonstrated that the cell surface glycoprotein CD147 on tumor cells mediates induction of matrix metalloproteinases (MMPs) by stromal cells in humans. However, for murine models such evidence remains elusive.
To address the impact of CD147 on MMP expression in the murine B16 melanoma model, we consequently stably knocked down CD147 expression in two B16 sublines. The CD147 knockdown remained stable under in vivo conditions as confirmed by immunohistochemistry. However, no differences in MMP-2, MMP-9 and MT1-MMP expression by stromal and tumor cells were detectable in CD147+ and CD147- tumors. Since the tumor microenvironment is a complex system, involving several cell types, the extracellular matrix and plethora soluble factors, we subsequently studied the role of murine CD147 in vitro. Coculture of melanoma cells with different fibroblast cell lines demonstrated that neither CD147+ nor CD147- B16 tumor cells altered the expression of MMP-2 or MMP-9 by the fibroblasts, although we could confirm the susceptibility of these fibroblasts for MMP induction.
At least for the murine B16 melanoma model, CD147 expression on tumor cells seems not to be crucial for MMP-2, MMP-9 and MT1-MMP induction on tumor-associated stromal cells.
已有确凿证据表明,人类肿瘤细胞表面糖蛋白CD147可介导基质细胞诱导基质金属蛋白酶(MMPs)的产生。然而,在小鼠模型中,此类证据仍不明确。
为研究CD147对小鼠B16黑色素瘤模型中MMP表达的影响,我们在两个B16亚系中稳定敲低了CD147的表达。免疫组化证实,在体内条件下,CD147的敲低效果稳定。然而,在CD147阳性和阴性肿瘤中,未检测到基质细胞和肿瘤细胞的MMP-2、MMP-9和MT1-MMP表达存在差异。由于肿瘤微环境是一个复杂系统,涉及多种细胞类型、细胞外基质和大量可溶性因子,我们随后在体外研究了小鼠CD147的作用。黑色素瘤细胞与不同成纤维细胞系共培养表明,CD147阳性和阴性的B16肿瘤细胞均未改变成纤维细胞中MMP-2或MMP-9的表达,尽管我们可以证实这些成纤维细胞对MMP诱导敏感。
至少对于小鼠B16黑色素瘤模型,肿瘤细胞上的CD147表达似乎对肿瘤相关基质细胞上MMP-2、MMP-9和MT1-MMP的诱导并不关键。