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"Spontaneous" Malignant Transformation in Vitro of Adult Mouse Cell Lines: Effect of Site of Implantation on Expression of Cell Antigenicity and Malignancy¹

Laboratories of Microbiology, The Children's Cancer Research Foundation, and The Department of Pathology, Harvard Medical School at the Children's Hospital, Boston, Massachusetts 02115

Cell cultures of normal adult mouse tissue origin, propagated in vitro for brief periods (34–85 days), exhibited "spontaneous" malignant transformation, as indicated by their ability to produce malignant metastasizing and transplantable tumors following injection into isogeneic and allogeneic normal adult hosts. This malignant transformation is associated with the appearance of a tumor-specific antigen.

The demonstration of antigenicity and malignancy of cultured cells depended on the site of implantation in the host. Primary intraperitoneal cell grafts usually resulted in death of the hosts, indicating no effective immune response had occurred. Primary subcutaneous cell grafts produced tumors which frequently regressed and immunized the host against a subsequent intraperitoneal graft. Therefore, malignancy of the cells is not only a property of the cell, but is also a function of cell graft-host interaction. A mechanism by which the site of cell implantation may affect the graft-host interaction is discussed.

¹ This investigation was supported in part by Research Grants C-6516 from the National Cancer Institute and FR-05526 from the Division of Research Facilities and Resources, NIH, USPHS.

Received 7/20/67. Accepted 11/28/67.