The 13762NF mammary adenocarcinoma is a syngeneic tumor of low immunogenicity and high metastatic potential in the Fischer 344 rat. Implantation of the 13762NF tumor on the iris with subsequent removal (enucleation) of tumor filled eyes, results in the establishment of dormant pulmonary metastases. Host defense mechanisms present in these enucleated rats inhibit the growth of extraocular tumor. The long term goals of the present proposal are to further characterize this new model, and to investigate the role played by host immune/defense mechanisms in the maintenance of the dormant state.
The specific aims of this proposal include the following: 1) To locate extraocular tumor cells in experimental animals at various times post-enucleation. This will be accomplished using an immunocytochemical technique of high specificity. 2) To determine the growth and/or metastatic potential of dormant pulmonary nodules. 3) To determine the specificity of the cytotoxic (static) mechanisms associated wtih maintenance of the dormant state. 4) To examine the effect of various manipulations of the hosts immune/defense mechanisms on the dormant state. In these studies we will examine the effects of irradiated and formalinized tumor cells, cyclosporin, cyclophosphamide, carrageenan and anti-asialo GM1 serum on the tumor dormant state. 5) To examine the role played by the spleen in maintenance and termination of the tumor dormant state. We believe that the enucleated rat model presented here, represents an ideal model for studying dormant metastases of a mammary adenocarcinoma. It is anticipated that further characterization of this model, and elucidation of experimental protocols capable of affecting dormancy, will yield information that can lead to additional studies. The latter will examine more specific mechanisms involved in the regulation of the tumor dormant state. Such studies should facilitate our ability to design therapeutic strategies which can be used in dealing with the problem of dormancy seen clinically.
