Interleukin-1 alpha and basic fibroblast growth factor induction of matrixmetalloproteinases and their inhibitors in osteosarcoma cells is modulatedby the metastasis associated protein CAPL

Background: Several recent investigations have shown that the expression of the CAPL protein seems to be of importance in the metastatic potential in some types of cancer. However, the mechanisms behind this and other biologi cal functions of CAPL are still largely unknown. The aim of the present wor k was to investigate whether CAPL could affect the expression of candidate proteolytic facilitators of the metastatic process, i.e. matrix metalloprot einases (MMPs) and their inhibitors (TIMPs). Materials and Methods: A highl y metastatic osteosarcoma cell-line with a high expression of CAPL was tran sfected with either a vector containing a ribozyme against this transcript or with the vector alone as a control. The expression of MMPs and TIMPs was investigated with ELISA and gelatin zymography. Results:: The cell-line wi th a low CAPL expression (III-14) responded to bFGF treatment by an increas ed synthesis of MMP-1 and MMP-9 and to Il-la treatment by an increased synt hesis of MMP-9. In contrast the cell-line with a high CAPL expression (pH b eta-1) did not respond with an altered expression of these MMPs. Neither of these two cell-lines responded with an altered expression of MMP-2. bFGF t reatment resulted in an increased expression of TIMP-1 in both cell-lines, while Il-la treatment resulted in a decreased production of TIMP-1 in pH be ta-1 cells, and III-14 cells were unaffected Conclusions: The CAPL protein expressed in cell-cultures appear to block the MMP induction by bFGF and Il -la. However, the induction of TIMP-1 by bFGF must proceed through a pathwa y different from the MMP induced pathway, i.e. a pathway unaffected by CAPL . In addition, CAPL appeared to act in synergy with Il-la to reduce the syn thesis of TIMP-1.