Abstract 3842: Culturing cancer cells on myoma tissue: Development of a novel fully human organotypic 3D invasion model applicable as a preclinical tool for cancer drug development.

Abstract

Abstract Cancer cell invasion has been traditionally studied in three-dimensional (3D) models composed of rat or mouse extracellular matrix (ECM) proteins. These models remain artificial due to the lack of various human ECM components and cell types that are present in the tumor microenvironment in vivo. Uterine leiomyoma (myoma) is a benign smooth muscle neoplasm with an incidence of 50% of all women over the age of 30 years in Finland. Due to its neoplasmic characterization myoma tissue provides an optimal microenvironment for studying cancer cell invasion and metastasis. Large amounts of myoma tissue are constantly removed from patients in routine operations and discarded, providing an unlimited amount of myoma tissue available for cancer research. We have previously characterized a novel fully human organotypic model where tongue squamous cell carcinoma cells (HSC-3) were cultured on myoma tissue, and demonstrated that the model was useful for studying HSC-3 cell invasion. We have now studied the model further by culturing various human breast and prostate cancer cell lines, including the breast cancer cell line MDA-MB-231 and the prostate cancer cell line PC-3 on myoma tissue. The myoma tissues were obtained from routine surgery after informed consent of the patients. HSC-3 cells were used as a reference cell line to confirm that the model works as expected. The cancer cells were cultured on top of human uterine leiomyoma tissue discs for 14 days, and invasion was assessed by histomorphometric analysis of the myoma tissue and measuring the release of appropriate biomarkers, such as degradation products of type I and type III collagen. A set of potential reference compounds, including inhibitors of matrix metalloproteinases, such as 1,10-phenanthroline, and cysteine proteases, such as E64, was tested for their effects on invasion capacity of the tested cancer cell lines. The results demonstrated that the tested breast and prostate cancer cell lines were highly invasive in the myoma tissue, and the used reference compounds inhibited the invasion of the cancer cells into the myoma tissue. Our results indicate that the myoma model can be applied for several cancer cell lines. We conclude that the established fully human organotypic 3D model is a reliable tool for demonstrating the efficacy of known reference compounds capable of inhibiting cancer cell invasion and metastasis, and it has the potential to be developed as a clinically predictive large scale method for identifying novel cancer drug candidates and confirming their efficacy in early preclinical phase of cancer drug development. Citation Format: Jukka P. Rissanen, Katja M. Fagerlund, Johanna M. Tuomela, Mari I. Suominen, Jussi M. Halleen, Tuula A. Salo. Culturing cancer cells on myoma tissue: Development of a novel fully human organotypic 3D invasion model applicable as a preclinical tool for cancer drug development. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3842. doi:10.1158/1538-7445.AM2013-3842