Finally, as with any in vitro system for the study of malignant tumors, the lack of an extracellular matrix (ECM) precludes the examination of any factors which could contribute further additive effects to tumor cell growth and metastatic potential; in the case of OS, the influences of MMP/TIMP interactions and ECM-associated growth factors on invasive potential have been examined but have not yet been fully elucidated (14, 15, 43, , , –47). This evidence concerns the gene TIMP1 and neoplasm.