The roles of epithelial-mesenchymal interactions and the innate immune response on the tumorigenicity of human prostate carcinoma cell lines grown in immuno-compromised mice.

ABSTRACT

BACKGROUND: Animal models are crucial to further our understanding of the mechanisms of (progressive) growth of prostatic cancer. MATERIALS AND METHODS: We have developed an intravital microscopic model based on the dorsal skinfold chamber technique in mice, allowing continuous measurements of growth and angiogenesis of small tumor spheroids. A histone H2B-GFP fusion protein has been introduced in our cell lines, allowing evaluation of mitotic and apoptotic indices. This system was used to evaluate the growth and angiogenesis of LnCAP, PC3 and DU145 tumor spheroids. RESULTS: LNCAP spheroids regressed rapidly, with complete tumor cell death within 7 days. PC3 spheroids regressed at a slower rate demonstrating a high apoptotic rate, though considerably lower than LNCAP. DU145 spheroids regressed the slowest, demonstrating considerably lower apoptotic rates and measurable mitotic rates. CONCLUSION: The inability to effectively the innate immune system by encapsulation prevents the survival of small human micro-tumor xenografts. Thus, the complex interactions between tumor cells and TAMs, which are pivotal in tumor biology, are extensively perturbed by "foreign" human tumor cells.