Invasion and Metastasis in Tumor Growth = Invasion and Metastasis in Tumor Growth

다국어 초록 (Multilingual Abstract)

Abundant new information has been gained by investigating the interaction of metastatic tumor cells with the extracellular matrix, especially with BMs. Attachment factors and cell surface receptors such as the laminin receptor may play a role in the anchoring of tumor cells to the endothelial BM. Local degradation of BMs by tumor cells has been observed by many investigators. A cascade of enzymes undoutedly facilitates this degradation. The enzymes are derived from both tumor cells and extraneoplastic sources. Among the most important proteases are the collagenases, plasminogen activators, cathepsins, and endoglycosidases. Understanding the steps involved in metastasis should allow for improved therapy. Although it is unrealistic to hope for a therapeutic modality that can interfere with all steps of the process, e.g. drugs that disrupt the cytoskeleton can retard invasion. The addition of specific inhibitors of glycosidases and proteases (2-acetamido-Zdeoxy- B -D-gluconolactone and leupeptin) can interfere with the ability of tumor cells to degrade ECM. The addition of protease inhibitors, such as leupeptin and pepstatin, to Adriamycin improved therapeutic efficacy in mice bearing Lewis lung carcinoma and M5076 sarcoma. Thus, inhibiting the invasive phenotype of cells can potentiate adjuvant therapy by a chemotherapeutic agent (11). Cellular heterogeneity during tumor progression has been demonstrated in a number of primary and metastatic tumors. The diversity and instability of tumor cell populations may lead to emergence of highly metastatic clones. Whether the increased metastatic potential is caused by new genetic information introduced into the tumor cell or by augmented expression of genes already turned on during the malignant transformation remains to be determined. Elucidation of the genetic mechanism responsible for induction of cells with metastatic properties will opn a new era in cancer biology.