Evidence suggests that the production of collagenases and other proteases in tumors may be necessary for subsequent metastasis. We have studied the effects of vitamin A (VA) and dexamethasone (Dex), known inhibitors of collagenase production, on the collagen metabolism of mouse mammary adenocarcinoma (C3HBA) and its capsule borne by C3H/Hej mice in relation to tumor invasion and metastasis. The major type of collagen synthesized or extracted from the capsule of the 3 groups was type 1. The specific activities of intracellular free ?14?C-proline, the hydroxylation levels of ?14?C-proline residues or specific activities of ?14?C-proline of collagen in each case were all similar between the capsule borne by treated and untreated hosts, suggesting that the observed 50% decreased collagen content of the capsule of Dex-treated hosts was due to the reduced collagen synthesis. A two-way analysis of variance and within-group analysis of our experimental data indicate that an inverse relationship occurred between the collagenase activity of the tumor and collagen content of the capsule. The unchanged protease activities of the tumor may be primarily responsible for the increased tumor invasion and metastases in Dex-treated hosts; the decreased collagen content may be secondary to that process. However, without that loss of collagen, there was no increased invasion and metastases. This has been evidenced by the morphological examination of the tumor which revealed that the tumors borne by VA-treated or untreated hosts showed a well-developed collagenized capsule at the inoculation site. In contrast, the Dex-treated hosts showed a thin and partially broken capsule, suggesting a distinctly more aggressive behavior of the tumor as revealed by invasion of neighboring structures and metastases to distant organs. Thus, the collagen metabolism of the capsule may be an indicator of proteolytic events within the tumor and the metastatic potential of the tumor. That, in turn, suggests the possibility of preventing metastasis by inhibiting the production of proteases, thereby localizing the tumor cells within the capsule. VA could be considered for that purpose. (N)
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