Influence of implantation site on formation of metastases.

It has been suggested that local factors at the site of growth of a primary tumor might influence the outcome of the metastatic process. Compilation of the data from the literature revealed that growth of tumor cells in the selective medium of the intraperitoneal cavity, of the lymph node and/or of the spleen leads to progression towards a population of cells with a higher metastatic capacity. In search for an experimental model with transplantable rodent tumors that could be used to study the influence of the anatomic site of an implant on the formation of spontaneous metastases, we have considered heterogeneity of microenvironmental conditions in the subcutaneous milieu. For the MO4 mouse fibrosarcoma, a primary tumor growing subcutaneously in the tail was highly metastatic to lymph nodes and lungs while it failed to produce metastases when growing in the pinna. Implantation of a spheroidal aggregate of MO4 tumor cells, alternatively in the tail and in the pinna of syngeneic C3H/He mice, might be an appropriate model, which is discussed in this review.