Abstract 5222: Metabolomic patterns of tumors and metastases of human colon cancer xenografts

Abstract

Abstract Prognostic assessment of colon cancer metastasis and intervention in metastatic disease represent critical clinical challenges. Metabolomic platforms now offer the potential for a systematic survey of the metabolic profile of tumor tissues, which may allow to link key metabolites to distinct aspects of tumor biology such as metastatic capacity. Here we addressed these issues by testing the hypothesis that metastatic disease is characterized by distinct metabolites. In preparation for subsequent analyses of human tumor samples from existing tissue collections, here we employed human colon cancer lines harboring metastatic capacities to induce cancer xenografts in mice. In a first set of experiments using human colon xenografts, and applying GC-MS based metabolomics technology, we characterized the metabolite patterns of the primary tumors and of liver metastases, as well as of the mouse spleens (organ of transplantation) and the mouse livers (main target organ of distant metastasis). Subjecting the metabolite data to a Principal Component Analysis resulted in the separation of the samples into four clusters discriminating on the one hand mouse from human tumor xenograft tissues. Furthermore, mouse spleen was easily separated from mouse liver. More importantly, we identified clearly distinct metabolomic clusters comprising the primary tumor samples vs. the liver metastasis although originating from the same human colon cancer cell line. These different metabolic profiles of primary tumors and metastases were highly reproducible between independent experiments and were conserved in primary tumors or metastases of different size, suggesting they offer a representation of distinct biological features, rather than reflect tumor cell mass or common features of the tumor cell microenvironment. In addition, defined metabolites were identified that are characteristic for particular mouse organs (spleen vs. liver), and for discrimination of mouse tissues vs. human xenograft tumors. Moreover, metabolites were identified that allow discrimination of the primary tumor vs. its corresponding liver metastasis, although both tissues originate from the same human colon cancer cells. We also addressed methodological topics, such as the influence of time until sample cryo-asservation, time of storage, size and amount of the tissue samples, and reproducibility in independent in vivo experiments, on the metabolomic patterns and specific metabolites. In summary, we identified metabolomic patterns as well as defined metabolites that allow discrimination of the primary tumor vs. its corresponding liver metastasis of colon cancer xenografts in mice. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5222. doi:10.1158/1538-7445.AM2011-5222