Invasion of malignant C3H mouse fibroblasts from aggregates transplanted into the auricles of syngenic mice.

Spheroid aggregates of malignant fibroblasts (MO4), shown to be invasive in vitro, were implanted subcutaneously into the auricle of the external ear of syngenic C3H mice. The course of early invasion into the surrounding tissues and the formation of tumours was studied in serial sections of auricles fixed 6 h to 30 days after implantation. MO4 cells are first observed to make contact with the surrounding tissues after 6 h. They exhibit, cytoplasmic extensions and spread from the original aggregate. During the first day invading MO4 cells preferentially follow tissue crevices created by the inoculation procedure. Later they also invade the surrounding tissues. Polymorphonuclear leucocytes, and later monocytes infiltrate the aggregate, which is completely destroyed after 4 days. Palpable tumours arise from MO4 cells that have left the original implant and invaded the tissues of the auricles. These observations indicate that invasion of malignant cells is important for the take of a transplant.