The Bulletín of Kanagawa Dental College

Vol. 36 No. 2       September- 2008

ISSN: 0385-1443      UBIC: 65

ABSTRACT

The invasion and metastasis of oral squamous cell carcinoma (SCC) are complex processes that require interaction between cancer cells and stromal cells. During mutual interaction, the secretion and activation of matrix metalloproteinases (MMPs) that degrade the extracellular matrix (ECM) are triggered. We previously showed that in an in vitro 3- dimensional (3-D) co-culture model, pro-MMP-9 (92-kDa) derived from oral SCC cell HSC-3, was converted into fully active-MMP-9 (67-kDa) with an MRC-5 fibroblast embedded in type 1 collagen gel, and that the cancer cells invaded the gel. In the present study, we attempt to further clarify the key proteinases or factor(s) as the SCC cells migrate into stromal tissue. The expression and activation of MMPs were detected with gelatin zymography and Western blot analysis. The mRNA expressions of the proteinases and various proteinase inducers of the cancer cell (HSC-3) as well as stromal cells (MRC-5) were examined by RT-PCR. We found that the HSC-3 cell migration into the matrigel was enhanced by MRC-5-derived soluble factor(s). Also, in a histological examination, we found that cancer-cells seeded onto type I collagen gel started to invade the gel in our in vitro 3-D invasion assay. Furthermore, soluble factor(s) from HSC-3 upregulated the expression of MMP-3, MMP-1, and MMP-7 genes from the MRC-5 fibroblasts, whereas the soluble factor(s) of MRC-5 increased the mRNA expression of MMP-1 on HSC-3. These results suggested that in this sophisticated in vitro model, cancer cell derived soluble factor(s) stimulated stromal fibroblasts to further produce proteinases that induce MMP-9 activation, and this was indispensable in cancer invasion. Key words: Cancer invasion / Matrix metalloproteinases / Stromal fibroblasts / In vitro 3-D invasion model.

| Volver |