Genomics and proteomics approaches to the study of cancer-stroma interactions
1 Department of Molecular Biology, School of Medicine (FAMERP), São José do Rio Preto, Brazil
2 Department of Biology, Instituto de Biociências, Letras e Ciências Exatas (IBILCE), São Paulo State University (UNESP), São José do Rio Preto, Brazil
3 Department of Otorhinolaryngology and Head and Neck Surgery, School of Medicine (FAMERP), São José do Rio Preto, Brazil
4 Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo (USP), São Paulo, Brazil
5 Department of Head and Neck Surgery, Arnaldo Vieira de Carvalho Hospital, São Paulo, Brazil
6 Division of Head and Neck Surgery, Department of Surgery, School of Medicine (USP), São Paulo, Brazil
7 Department of Head and Neck Surgery, Heliópolis Hospital, São Paulo, Brazil
8 Department of Biology and Zootechny, Faculty of Engineering of Ilha Solteria (UNESP), Ilha Solteira, Brazil
9 Author list and addresses presented in the Acknowledgements
BMC Medical Genomics 2010, 3:14 doi:10.1186/1755-8794-3-14Published: 4 May 2010
The development and progression of cancer depend on its genetic characteristics as well as on the interactions with its microenvironment. Understanding these interactions may contribute to diagnostic and prognostic evaluations and to the development of new cancer therapies. Aiming to investigate potential mechanisms by which the tumor microenvironment might contribute to a cancer phenotype, we evaluated soluble paracrine factors produced by stromal and neoplastic cells which may influence proliferation and gene and protein expression.
The study was carried out on the epithelial cancer cell line (Hep-2) and fibroblasts isolated from a primary oral cancer. We combined a conditioned-medium technique with subtraction hybridization approach, quantitative PCR and proteomics, in order to evaluate gene and protein expression influenced by soluble paracrine factors produced by stromal and neoplastic cells.
We observed that conditioned medium from fibroblast cultures (FCM) inhibited proliferation and induced apoptosis in Hep-2 cells. In neoplastic cells, 41 genes and 5 proteins exhibited changes in expression levels in response to FCM and, in fibroblasts, 17 genes and 2 proteins showed down-regulation in response to conditioned medium from Hep-2 cells (HCM). Nine genes were selected and the expression results of 6 down-regulated genes (ARID4A, CALR, GNB2L1, RNF10, SQSTM1, USP9X) were validated by real time PCR.
A significant and common denominator in the results was the potential induction of signaling changes associated with immune or inflammatory response in the absence of a specific protein.