Investigation of tumor-tumor interactions in a double human cervical carcinoma xenograft model in nude mice

Abstract

Tumor-tumor distant interactions within one organism are of major clinical relevance determining clinical outcome. To investigate this poorly understood phenomenon, a double human cervical xenograft model in nude mice was developed. A first tumor was induced subcutaneously by injection of human papillomavirus positive cervical carcinoma cells into the mouse lower right flank and 3 weeks later, animals were challenged with the same tumor cell line injected subcutaneously into the upper left flank. These tumors had no direct physical contact and we found no systemic changes induced by the primary tumor affecting the growth of a secondary tumor. However, ablation of the primary tumor by local treatment with cidofovir, a nucleotide analogue with known antiviral and antiproliferative properties, resulted not only in a local antitumor effect but also in a temporary far-reaching effect leading to retarded growth of the challenged tumor. Cidofovir far-reaching effects were linked to a reduced tumor-driven inflammation, to increased anti-tumor immune responses, and could not be enhanced by co-administration with immune stimulating adjuvants. Our findings point to the potential use of cidofovir in novel therapeutic strategies aiming to kill tumor cells as well as to influence the immune system to fight cancer.