Effect of Tumor Cells on Pre-Existing Collagen and on Collagen Production by Normal Cells Grown in Diffusion Chambers

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Abstract
Experiments were designed to test the effect of tumors on collagen production and on pre-existing collagen of normal tissues. Both mouse and rat tumors and normal tissues were used. The cells of mouse lymphomas L#1 and L#2 and of a mouse tumor derived from liver, Hepatoma 129(P), were freed of “contaminating” normal stroma by rapid transplantation in diffusion chambers. The tumor cells were then recombined in diffusion chambers with normal mouse peritoneal cells and normal mouse connective tissue. Control chambers containing normal cells alone were also prepared. After 4 weeks of growth, the total collagen in the chambers was estimated by the determination of total hydroxyproline. To test the effect of tumor tissue growing outside the chamber on tissue growing within the chamber, rat connective tissue and Novikoff hepatoma were placed in diffusion chambers implanted subcutaneously in the rat. Some chambers were dipped in a slurry of the Novikoff hepatoma or the Walker carcinosarcoma 256 before subcutaneous implantation so that the chambers were quickly surrounded by the tumor mass. After 3 weeks, the chambers containing connective tissue were analyzed for hydroxyproline (as an estimate of total collagen), while those containing the Novikoff hepatoma were analyzed for deoxyribonucleic acid (as an estimate of total cell number). The results showed that the mouse tumors did not have the capacity to destroy pre-existing collagen. However, the total collagen found in the chambers was usually decreased in the presence of the tumor cells. This decrease appeared to be due to an inhibition of the proliferation of collagen-producing cells rather than to the suppression of collagen synthesis.