Interaction of B16 Malignant Melanoma Tumor Cells with the Murine Mesentery in Vitro

We have used organ cultures of murine mesentery as a model system to investigate the mechanisms by which B16-F10 melanoma cells invade normal tissues. The mesentery has the advantage of being a real tissue, consisting of a loose connective tissue, containing a normal complement of stromal cells and extracellular matrix, covered by a continuous epithelium of squamous mesothelial cells which are separated from the connective tissue by a laminin-containing basement membrane. B16-F10 cells seeded onto the mesentery in vitro cause a local retraction of the mesothelial cells exposing the underlying basement membrane onto which the tumor cells spread. Direct contact between the tumor cells and the margins of the mesothelial cells is required to induce retraction. Most of the B16 cells remain on the surface of the mesentery where they spread on the basement membrane without disrupting it. A few B16 cells penetrate the basement membrane and invade the connective tissue interior of the mesentery where they flatten out and assume a fibroblastic morphology. Tumor cells within the connective tissue may continue to translocate and they adhere to and move along the fibers of the connective tissue extracellular matrix without appearing to destroy or disrupt them.