Collagenase Inhibitors Retarding Invasion of a Human Tumor in Nude Mice

Abstract

Tumor invasion has been correlated with the ability of tumor cells to produce collagenolytic enzymes which are capable of degrading normal host tissues. However, the human small cell carcinoma implanted subcutaneously and growing progressively in athymic (nude) mice produced large quantities of collagenase but did not appear to significantly infiltrate adjacent host tissue. In comparison, subcutaneously implanted murine Lewis lung tumors produced similar quantities of collagenase and were locally invasive. The human tumors were surrounded by a compact layer of fibroblast cells in a fibrous matrix. This fibrous sheath exhibited anticollagenase activity and indicated a mechanism of host tissue resistance to invasion via the formation of inhibitors to degradative enzymes produced by tumor cells.

Species-Specific Fibroblasts Required for Triggering Invasiveness of Partially Transformed Oral Keratinocytes

“…27 The species specificity described above could be related to the differences in cytokine and collagenase production between mouse, rat, and human species. 43,44 The fact that conditioned medium from co-cultures of DOK cells and human fibroblasts could induce DOK invasiveness in mouse fibroblast-containing matrix points more to the lack of appropriately induced growth factors in mouse fibroblasts by human DOK cells. This might be due to a deficiency in the cross-talk between human keratinocytes and mouse fibroblasts.…”

Orthotopic implantation of human colon carcinomas into nude mice provides a valuable model for the biology and therapy of metastasis

“…Most solid tumors grafted into the subcutis of nude mice grow locally but show limited invasiveness. This lack of invasion, as well as the consequent lack of metastasis, has been often associated with the development of a dense, fibrous capsule around the tumor [22,49]. The metastatic capacity of human tumor cells implanted subcutaneously into the nude mouse has been found to correlate with invasion of the body wall [14,15].…”

Organ specificity of tumor metastasis: role of preferential adhesion, invasion and growth of malignant cells at specific secondary sites

“…Such indirect effects of tumors on surrounding tissues, and vice versa, have been seen in a variety of tumor systems. De Vore et al [244] noted that the invasive behaviors of human small cell carcinoma cells were limited at s.c. sites in nude mice by a fibroblastic capsule around the tumor. The tumor-associated fibroblasts were subsequently shown to release collagenase inhibitors that were active against the human tumor collagenases.…”