Reciprocal modulation of mesenchymal stem cells and tumor cells promotes lung cancer metastasis
Giulia Fregni,
Mathieu Quinodoz,
Emely Möller,
Joanna Vuille,
Sabine Galland,
Carlo Fusco,
Patricia Martin,
Igor Letovanec,
Paolo Provero,
Carlo Rivolta,
Nicolo Riggi,
Ivan Stamenkovic
Affiliations
Giulia Fregni
Experimental Pathology Service, CHUV and University of Lausanne, 1011, Switzerland
Mathieu Quinodoz
Department of Computational Biology, Unit of Medical Genetics, University of Lausanne, 1011, Switzerland
Emely Möller
Experimental Pathology Service, CHUV and University of Lausanne, 1011, Switzerland
Joanna Vuille
Experimental Pathology Service, CHUV and University of Lausanne, 1011, Switzerland
Sabine Galland
Experimental Pathology Service, CHUV and University of Lausanne, 1011, Switzerland
Carlo Fusco
Experimental Pathology Service, CHUV and University of Lausanne, 1011, Switzerland
Patricia Martin
Experimental Pathology Service, CHUV and University of Lausanne, 1011, Switzerland
Igor Letovanec
Experimental Pathology Service, CHUV and University of Lausanne, 1011, Switzerland
Paolo Provero
Center for Translational Genomics and Bioinformatics, San Raffaele Scientific Institute, IRCCS, Milan20132, Italy; Dept. of Molecular Biotechnology and Health Sciences, University of Turin, 10126 Turin, Italy
Carlo Rivolta
Department of Computational Biology, Unit of Medical Genetics, University of Lausanne, 1011, Switzerland; Department of Genetics and Genome Biology, University of Leicester, Leicester LE1 9HN, UK
Nicolo Riggi
Experimental Pathology Service, CHUV and University of Lausanne, 1011, Switzerland
Ivan Stamenkovic
Experimental Pathology Service, CHUV and University of Lausanne, 1011, Switzerland; Corresponding author.
Metastasis is a multi-step process in which direct crosstalk between cancer cells and their microenvironment plays a key role. Here, we assessed the effect of paired tumor-associated and normal lung tissue mesenchymal stem cells (MSCs) on the growth and dissemination of primary human lung carcinoma cells isolated from the same patients. We show that the tumor microenvironment modulates MSC gene expression and identify a four-gene MSC signature that is functionally implicated in promoting metastasis. We also demonstrate that tumor-associated MSCs induce the expression of genes associated with an aggressive phenotype in primary lung cancer cells and selectively promote their dissemination rather than local growth. Our observations provide insight into mechanisms by which the stroma promotes lung cancer metastasis. Keywords: Tumor-associated MSCs, lung cancer, metastasis, GREM1, LOXL2, ADAMTS12, ITGA11
