구강 편평세포암종의 침윤성 성장에 미치는 섬유모세포의 영향 Effects of Stromal Fibroblasts on the Invasiveness of Oral Squamous Cell Carcinoma
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Matrix metalloproLeases(MMPs) a re a family of zinc dependent enzymes with the capacity to degrade extracellular matrix prote ins. MMPs express ion correlates with cancer cell invasiveness and metas taslS The purpose of our sωdy was t。 determine the role 0 1' stroma l fïbrob lasts in ca ncer cell invasi on by examining the expression and activity of MMP-2 and -9 We used a YD- lOB squalllous ca rcinoma cell line that was est a blished in Yonsei Univer s ity ‘ College 0 1' Dentistry. We then appli ed two types of s lrolllal fibroblastsdel‘ ived from normal gingival tissue and cancer supporting ti ss ue Morphologic examination of fïbroblas ls was carried out by rnicroscopy and doubling time was measured by MTI assay . YD-lOB cells were cultured by lh ree-d imensional culture using collagen gel with two types of flbroblasts To examine the stromal - mesenchyma l inleraclion. we used a direct co-cul tu re system between YD-IOB cells and fibroblasts. Gelatin zymography was performed to exa llline MMP-2 a ncl 9 activit ies. We found that cancer-derived fibroblasts di splay stel late-shaped cells wi th many cyLopl asmic processes. whereas normal gingi val fibroblasts were spindle shaped. The c1oubling time of bOLh lïbroblasLs was not statistically different. Three-dimensional co-culture 0 1' ca ncer cells with ca n cer- c1erived fïbroblasts induced the formation 0 1' multi - Iayered atypical cells, as compared to culturing with normal gin gival f lbrobl asts Both three-c1 imens ional culture ti ss ues inclucecl the invasive gro￦th of cancer cells into the dermal eq uival enLs . Gelatin zymography s howecl that gelatinolytic activity of MMP-2 was activaterl in both co-culture models. However , MMP-9 ac li vity was not a lterecl in YD-lOB carcinoma cells In conclusion. enhanced MMP-2 activity was inc1 uced by boLh cance r- c1eri vecl a ncl norlllal gingival fibroblasts. suggesting that the potential to invacle by stromal fibroblasts was noL l imilecl to ca ncer- c1 eri ved lïbroblasts