Effects of vitamin A and dexamethasone on capsule collagen metabolism in mouse mammary adenocarcinoma.

It was previously shown that the administration of dexamethasone (Dex) to mice bearing mammary adenocarcinoma caused the collagen content of the tumor capsule to be decreased by 50%, but collagenase and other neutral protease activities of the tumor were the same as in the controls. These events occurred with distinctly increased tumor invasion and metastasis. The present communication reports on the characterization of capsule collagen and the effects of agents [vitamin A (VA) and Dex] on capsule collagen metabolism and presents further evidence concerning the possible mechanisms by which the collagen content of the capsule was decreased in the Dex-treated hosts. The collagen extracted from capsules of untreated controls and mice (C3H/HeJ) treated with VA or Dex was primarily type I, as judged by the migration of protein bands in sodium dodecylsulfate-polyacrylamide gel electrophoresis and by patterns of elution peaks from an octadecyl C-18 column. The amino acid compositions of type I collagen of the capsule of treated and untreated controls were similar but not identical to those of mouse skin and guinea pig skin type I collagens. The specific activity of intracellular free [14C] proline, the extent of hydroxylation of [14C]proline residues of collagen, and the specific activity of [14C]hydroxyproline and proline in each case were similar in treated and in untreated controls. These results suggest that the observed 45% decrease in the conversion of [14C]proline into protein-bound [14C]hydroxyproline of the Dex-treated hosts apparently was due to decreased collagen synthesis. The data also suggest that the most critical effects of Dex on tumor invasion and metastasis appeared to occur at an early stage before full formation of the collagenous extracellular matrix.