Tumor cell interactions with the extracellular matrix during invasion and metastasis.

Recent findings have produced great strides in developing an understanding of the molecular events involved in processes necessary for tumor cell invasion and subsequent metastasis formation. This information has been useful in developing new targets for therapeutic intervention such as disruption of tumor cell attachment by peptide analogues of cell adhesion molecules and the use of protease inhibitors to limit extracellular matrix proteolysis required for tumor cell invasion. Future efforts must focus on how the events of cell attachment, matrix proteolysis, and cell migration are controlled and integrated. This requires a better understanding of the transcriptional controls and cell signaling mechanisms that are involved in these events. Preliminary findings suggest that cell-matrix interactions influence gene expression and that the protease inhibitor balance can greatly influence cell-matrix interactions. Therefore it appears that all three steps in the invasive process are linked and interdependent. While this complicates the study of these processes, it is our belief that understanding this interdependence is critical for further development of metastasis research.