Abstract 1333: Organ specific biomatrix scaffolds for ex vivo characterization of colorectal cancer metastases

Abstract

Abstract Colorectal cancer is the second leading cause of cancer-related deaths in the United States with more than 140,000 new cases being diagnosed this year. However, morbidity and mortality is not generally caused by the primary tumor, but by metastases to other organs. There are few models in which to study colorectal cancer metastasis, either in two-dimensional (2D) monolayer tissue culture or in animal xenografts. Both of these models have limitations. Standard 2D tissue culture, though inexpensive and accessible, poorly mimics the metastatic process and xenograft models are costly and technically challenging. Two of the most common sites of colorectal metastasis are the liver and lungs, however, there are few ex vivo models in which to study metastases to these sites. Advances in materials science have led to the development of ex vivo tissue specific models of extracellular matrices (ECM). We have utilized a novel material, biomatrix scaffolds, to engineer a colorectal cancer metastasis ex vivo model. We hypothesized that through the use of liver and lung specific biomatrix, (1) we can better characterize the colorectal cancer metastatic process by mimicking the organ specific microenvironment and (2) more accurately determine the response to therapeutic agents to treat metastases. In this study, we characterized biomatrix derived from rat liver and lung as a growth substrate for human colon cancer cell lines. We used the human colon cancer derived cell lines: HT29, SW480, CaCo2 and Lovo. Chemotherapeutic response to oxaliplatin, irinotecan and 5-fluorouracil for these cell lines grown on biomatrix was examined. We also used primary cultures of colorectal cancer metastases derived from patient samples. The biomatrix scaffolds were generated through decellularization of rat liver or lungs. We preformed mass spectrometry and determined the ECM composition and the associated growth factors found in lysates of liver and lung remain bound to the biomatrix in concentrations similar to those found in vivo. Colorectal cancer cell lines demonstrated different growth rates and morphologies when grown on biomatrix, resulting in organized, 3-dimenasional growth of non-hollow spheroids several hundred microns in diameter. We demonstrated differential responses to chemotherapeutics and observed differential gene expression via microarray analysis when colorectal cancer cell lines were grown on biomatrix compared to plastic, collagen, or matrigel. We also demonstrated increased tumor cell colony formation in primary cultures of patient derived colorectal metastases on biomatrix compared to plastic or collagen. In conclusion, we have developed a decellularized tissue material, biomatrix, that can provide an ex vivo model of colorectal cancer metastasis to aid in therapeutic drug development and genetic characterization of metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1333. doi:1538-7445.AM2012-1333