Conclusions
Our study, as shown in Figure 6, demonstrates that the MMP-2 gene,
upstream of Src, regulates Src kinase activity by suppressing CHK/MATK,
the endogenous Src inhibitor, in osteosarcoma cells. Furthermore, the
enhanced cell migration caused by sublethal doxorubicin concentrations
can be overcome by overexpressing CHK/MATK or inactivating the MMP-2
gene. Consequently, we propose that intracellular/nuclear MMP-2
represents an additional target as it affects the gene and protein
expression of the tumor suppressor CHK/MATK in osteosarcoma. We
hypothesize that inhibiting intracellular/nuclear MMP-2, resulting in
CHK/MATK overexpression, will improve clinical outcomes in osteosarcoma
patients treated with lower doses of doxorubicin.