The matrix of human breast tumor cells is mitogenic for fibroblasts.

The basis of the scirrhous reaction to human breast carcinoma was investigated. When normal human skin fibroblasts were plated on the preformed extracellular matrix of human breast tumor cells, a remarkable series of changes was observed. The matrix of the tumor cells was mitogenic for the fibroblasts. An increased growth rate and a fourfold increase in cell density was observed. There was also a change in cell morphology and in the pattern in which the cells grew, with an apparent loss of contact inhibition. The spindle-shaped fibroblasts became more elliptical and grew in a series of whorls and dense ridges with spaces between them. These observations were made with the use of newborn foreskin fibroblasts and the matrix of an established line of human breast cancer cells, ZR75-1. No such effect was seen when fibroblasts were plated on their own preformed matrix, on the matrixes of other cell types, on various type-specific collagen gels, or on a combination of collagen and fibronectin or when fibroblasts were grown in media conditioned by the ZR75-1 cells. A floating tumor cell matrix added to the cell media also did not provide the mitogenic stimulus. Apparently, fibroblasts required direct contact with the tumor cell matrix for the mitogenic response to occur. In vivo, the matrix of breast tumor cells may modulate the growth and the morphology of host stromal cells. Collagen is a major synthetic product of fibroblasts. The stimulation of stromal cells to proliferate by adjacent breast tumor matrix may be the basis of the desmoplastic reaction, the intense fibrotic response associated with human breast cancer.