Morphological studies on V2 carcinoma invasion and tumor-associated connective tissue changes in the rabbit mesentery

The mesentery is a duplicature of the peritoneum consisting of loose connective tissue and covered on both sides by mesothelium. Rabbit V2 carcinoma cells implanted i.p. adhere to the mesenteric surface between contracted mesothelial cells. While invasion from these sites sets in, progressive changes of the connective tissue, reflecting fibroblast stimulation, become apparent and comprise multiplication of connective tissue cells, transformation of fibrocytes into fibroblasts, and enhanced production of fibrillar and nonfibrillar constituents of the extracellular matrix. Tumor invasion into this increasingly dense tissue proceeds in 2 ways. (a) Single cells penetrate into and locomote within the interior, where they divide and give rise to nodules which become surrounded by zones of tissue destruction. (b) Proliferation of surface-attached tumor cells results in the formation of nodules which, preceded by zones of tissue damage, extend into the interior. While evidence for lytic effects in the microenvironment of single tumor cells is lacking, degradation of the fibrillar extracellular matrix is regularly found around tumor nodules and indicates a collective lytic action achieved by tumor cells and, possibly, host cells. These morphological findings are discussed in relation to published bio- and histochemical data on spread of the V2 carcinoma.