title: Nesting of colon and ovarian cancer cells in the endothelial niche is associated with alterations in glycan and lipid metabolism.
abstract: The metabolic phenotype of a cancer cell is determined by its genetic makeup and microenvironment, which dynamically modulates the tumor landscape. The endothelial cells provide both a promoting and protective microenvironment - a niche for cancer cells. Although metabolic alterations associated with cancer and its progression have been fairly defined, there is a significant gap in our understanding of cancer metabolism in context of its microenvironment. We deployed an in vitro co-culture system based on direct contact of cancer cells with endothelial cells (E4+EC), mimicking the tumor microenvironment. Metabolism of colon (HTC15 and HTC116) and ovarian (OVCAR3 and SKOV3) cancer cell lines was profiled with non-targeted metabolic approaches at different time points in the first 48 hours after co-culture was established. We found significant, coherent and non-cell line specific changes in fatty acids, glycerophospholipids and carbohydrates over time, induced by endothelial cell contact. The metabolic patterns pinpoint alterations in hexosamine biosynthetic pathway, glycosylation and lipid metabolism as crucial for cancer - endothelial cells interaction. We demonstrated that "Warburg effect" is not modulated in the initial stage of nesting of cancer cell in the endothelial niche. Our study provides novel insight into cancer cell metabolism in the context of the endothelial microenvironment.
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar, Qatar-Foundation, P.O. Box 24144, Doha, Qatar.
authors.forename: Anna
authors.initials: A
authors.lastname: Halama
authors.affiliation: Stem Cell and Microenvironment Laboratory, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar.|Department of Genetic Medicine, Weill Cornell Medicine-Qatar, New York, NY 10065, USA.|Translational Medicine Division-Research Department, Sidra Medical and Research Center, P.O. Box 26999, Doha, Qatar.
authors.forename: Bella S
authors.initials: BS
authors.lastname: Guerrouahen
authors.affiliation: Stem Cell and Microenvironment Laboratory, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar.|Department of Genetic Medicine, Weill Cornell Medicine-Qatar, New York, NY 10065, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Pasquier
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar, Qatar-Foundation, P.O. Box 24144, Doha, Qatar.
authors.forename: Noothan J
authors.initials: NJ
authors.lastname: Satheesh
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar, Qatar-Foundation, P.O. Box 24144, Doha, Qatar.|Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Suhre
authors.affiliation: Stem Cell and Microenvironment Laboratory, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar.|Department of Genetic Medicine, Weill Cornell Medicine-Qatar, New York, NY 10065, USA.|Department of Genetic Medicine and Obstetrics and Gynecology, Weill Cornell Medical College, Stem Cell and Microenvironment Laboratory, Weill Cornell Medical College in Qatar, Qatar-Foundation, P.O. Box 24144, Doha, Qatar.
authors.forename: Arash
authors.initials: A
authors.lastname: Rafii
mesh_terms: D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003110:Colonic Neoplasms / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D006031:Glycosylation; D006801:Humans; D050356:Lipid Metabolism; D010051:Ovarian Neoplasms / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism*; D059016:Tumor Microenvironment
chemical_list: D011134:Polysaccharides