This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Mintz, B. Articles by Silvers, W. K. Search for Related Content PubMed PubMed Citation Articles by Mintz, B. Articles by Silvers, W. K.

Accelerated Growth of Melanomas after Specific Immune Destruction of Tumor Stroma in a Mouse Model¹

Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111

Destruction of the entire stroma in a tumor could provide a stringent test of the prospects for tumor eradication in a single treatment. This possibility was investigated by experimental immune destruction of the stroma in a mouse melanoma model. Melanomas were first produced by grafting skin from transgenic C57BL/6 females of high-melanoma susceptibility to low-susceptibility transgenic males so that the malignant cells would be genetically female and the stromal cells genetically male. Subcutaneous transplant lines were then established from the melanotic and the amelanotic zones of such a melanoma and were carried in transgenic male hosts to ensure the male composition of the stroma. Thus, the male-specific H-Y histocompatibility antigen, which is ubiquitously expressed on male cells, could provide the target for an immune attack against the stroma. The transplant lines were next passaged once in transgenic females preimmunized against the H-Y antigen by having received and rejected a graft of C57BL/6 nontransgenic male skin. The antistromal immune response of these hosts did not prevent recovery of the tumors, which required a substantially prolonged latency. However, after retransplantation to nonimmunized males and females, the latency was markedly shortened from the original level. Thus, the treatment had indirectly selected for more rapidly growing tumor cells and hastened malignant progression.

¹ This work was supported by an American Cancer Society Special Research Grant for Metastatic Melanoma (to B. M.) and by USPHS Grants CA-06927 and RR-05539 to the Fox Chase Cancer Center.

² To whom requests for reprints should be addressed, at Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111.

³ Visiting Scientist from the University of Pennsylvania.

Received 11/14/95. Accepted 12/21/95.