Mouse Model Exhibiting the Phenomenon of Inhibition of Tumor Growth by Tumor Mass

An animal model that exhibited the phenomenon of the inhibition of tumor growth by tumor mass was developed (5,6). Several passages of the Lewis lung carcinoma (LLC) in C57B6 mice, with constant selection for the occurrence of low numbers of metastases in the lungs, resulted in an LLC-low metastatic (LLC-LM) phenotype. This LLC-LM tumor typically grew from an inoculum of 1 x 106 cells in the subcutaneous dorsum of mice, to a 1500-mm3 primary tumor in 2 wk. Within 13-21 d after resection of the primary LLC-LM tumors, the lungs of resected mice filled with neovascularized metastases. Lung weights, which correlated with tumor burden, were increased by >400%, compared with mice with intact primary tumors. L ungs of mice with unresected primary tumors were free of metastases (6). Thus, in this model, the presence of the primary tumor is associated with suppression of the growth of its remote metastases. Comparable results were seen with SCID mice lacking both T- and B-cell populations, indicating that inhibition of metastases in this model was not dependent on intact immune system metastases (6). O'Reilly et al. (6) fractionated biological fluids of animals with LLC-LM, to determine if these fluids contained factors that inhibited the proliferation of bovine capillary endothelial (BCE) cells stimulated by bFGF in vitro. Using this system, mouse AP, a 38-kDa protein, was identified and isolated from both serum and urine of LLC-LM-bearing mice.

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