Comparative studies of two types of “spontaneous” malignant alteration of ST/A mouse lung fibroblasts propagated in vitro

Summary Two types of apparently spontaneous malignant alterations of fibroblastlike ST/a mouse lung cells (ST-L cells) grown in vitro are described. One type is characterized by a high tumorigenic potential of the altered cells in nonconditioned syngeneic recipients, a fibro-blastlike morphology with cell surface showing very few microvilli by scanning electron-microscopy (SEM), and a growth pattern typical of nontransformed cells. These cells were described as R⁻ cells. The other type is characterized by a low tumorigenic potential in nonconditioned, immunocompetent syngeneic recipients, rounding up of the cells which by SEM showed numerous microvilli on the surface, and a growth pattern typical of transformed cells. These cells were described as round cells or R⁺ cells. In immunoincompetent mice, R⁺ cells readily produced sarcomas, which grew faster than those produced by R⁻ cells. Both types of ST-L cells expressed murine leukemia virus (MuLV) when tested in a peroxidase anti-p30 plaque test. The concentration of murine leukemia virus envelope glycoprotein (gp70) has previously (5) been shown to be threefold higher in R⁺ cells compared to R⁻ cells. Furthermore, round-cell transformation was accompanied by the development of crossreacting rejection antigens protective against a secondary challenge with Ehrlich ascites tumor and with syngeneic dimethylbenzanthracene induced ST/a mouse leukemia (STABAL). A similar protection was obtained by preimmunization with a cloned embryonic feral mouse cell line (SC-1) infected with ST-L virus as well as with virus-free SC-1 cells, suggesting the presence of rejection antigens both of viral (gp70) and nonviral origin. Sponsored by the Danish Cancer Society. Supported by the Kankerfonds van de Algemene Spaar-en Lijfrentekas. The SC-1 cell line was originally provided by contract E-73-2001-N01 within the Special Virus-Cancer Program NIH, USPHS, through the courtesy of Walter A. Nelson-Rees, Naval Biomedical Research Laboratory, Oakland, California, and Wallace P. Rowe, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland. The financial support of the Daell Foundation, the Schepler Foundation, the Jorgen Holm Foundation and the Danish National Research Foundation is gratefully acknowledged.