Gene expression profiling of normal human pulmonary fibroblasts following coculture with non-small-cell lung cancer cells reveals alterations related to matrix degradation, angiogenesis, cell growth and survival

• Published in: Oncogene Vol. 22; no. 52; pp. 8487 - 8497
• Main Authors: FROMIGUE, Olivia, LOUIS, Krystel, MARI, Bernard, DAYEM, Manal, MILANINI, Julie, PAGES, Gilles, TARTARE-DECKERT, Sophie, PONZIO, Gilles, HOFMAN, Paul, BARBRY, Pascal, AUBERGER, Patrick
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 20.11.2003; Nature Publishing Group; Nature Publishing Group [1987-....]
• Subjects: Angiogenesis; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Cell differentiation, maturation, development, hematopoiesis; Cell Division - genetics; Cell Division - physiology; Cell growth; Cell physiology; Cell Survival; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Coculture Techniques; Deoxyribonucleic acid; DNA; DNA microarrays; Endocrinology and metabolism; Extracellular Matrix - genetics; Extracellular Matrix - metabolism; Fibroblasts; Fibroblasts - metabolism; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Human health and pathology; Invasiveness; Kinases; Life Sciences; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Medical prognosis; Medical sciences; Microenvironments; Models, Biological; Molecular and cellular biology; Molecular modelling; Neovascularization, Pathologic - genetics; Neovascularization, Pathologic - metabolism; Non-small cell lung carcinoma; Pneumology; Proteinase inhibitors; Stromal Cells; Transcription; Transcriptomes; Tumor cells; Tumorigenesis; Tumors of the respiratory system and mediastinum; France; Human; Lung disease; desmopiasia; cDNA arrays; Respiratory disease; Growth; Lung cancer; Stroma; Malignant tumor; non-small cell lung carcinoma; Normal; Carcinogenesis; Survival; Angiogenesis; coculture; Complementary DNA; Bronchus disease; tumor-stroma; Fibroblast; stromelysin-3
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1206918

Increasing evidence supports a major role for the microenvironment in carcinoma formation and progression. The influence of the stroma is partly mediated by signalling between epithelial tumor cells and neighboring fibroblasts. However, the molecular mechanisms underlying these interactions are largely unknown. To mimic the initial steps of invasive carcinoma in which tumor cells come in contact with normal stromal cells, we used a coculture model of non-small-cell lung cancer tumor cells and normal pulmonary fibroblasts. Using DNA filter arrays, we first analysed the overall modification of gene expression profile after a 24 h period of coculture. Next, we focused our interest on the transcriptome of the purified fibroblastic fraction of coculture using both DNA filter arrays and a laboratory-made DNA microarray. These experiments allowed the identification of a set of modulated genes coding for growth and survival factors, angiogenic factors, proteases and protease inhibitors, transmembrane receptors, kinases and transcription regulators that can potentially affect the regulation of matrix degradation, angiogenesis, invasion, cell growth and survival. This study represents to our knowledge the first attempt to dissect early global gene transcription occurring in a tumor-stroma coculture model and should help to understand better some of the molecular mechanisms involved in heterotypic signalling between epithelial tumor cells and fibroblasts.