Multi-omics Analysis Reveals Adipose-tumor Crosstalk in Patients with Colorectal Cancer
| Autor: | Hans-Ulrich Kauczor, Johanna Nattenmüller, Martin Schneider, Stephen D. Hursting, Christy A. Warby, Biljana Gigic, Caroline Himbert, Alexis Ulrich, Peter Schirmacher, Jennifer Ose, Clare Abbenhardt-Martin, Richard Viskochil, Thomas Simon, Nina Habermann, Audrey Gicquiau, Magnus von Knebel-Doeberitz, Andrea Gsur, Juergen Boehm, Dieuwertje E. Kok, Augustin Scalbert, Tengda Lin, Pekka Keski-Rahkonen, David Achaintre, Matty P. Weijenberg, Kenneth M. Boucher, Cornelia M. Ulrich, Mariam Haffa, Esther Herpel, Andreana N. Holowatyj, Laura W. Bowers, Per M. Ueland, Dominique Scherer, Petra Schrotz-King, Matthias Kloor |
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| Přispěvatelé: | RS: GROW - R1 - Prevention, Epidemiologie |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
tissue macrophages EXPRESSION Cancer Research Peroxisome proliferator-activated receptor gamma obesity Nutrition and Disease Carcinogenesis Colorectal cancer INHIBITION Adipose tissue Intra-Abdominal Fat serum c-peptide 03 medical and health sciences 0302 clinical medicine INFLAMMATION Fibrosis Voeding en Ziekte Tumor Microenvironment medicine Life Science Humans Serum amyloid A Receptor VLAG RISK colon business.industry medicine.disease modulation 030104 developmental biology Adipose Tissue Oncology Adipogenesis FAT 030220 oncology & carcinogenesis Cancer research GPVI Colorectal Neoplasms business |
| Zdroj: | Cancer Prevention Research, 13(10), 817-828 Cancer Prevention Research 13 (2020) 10 Cancer prevention research, 13(10), 817-828. American Association for Cancer Research Inc. |
| ISSN: | 1940-6215 1940-6207 |
| Popis: | Obesity and obesity-driven cancer rates are continuing to rise worldwide. We hypothesize that adipocyte–colonocyte interactions are a key driver of obesity-associated cancers. To understand the clinical relevance of visceral adipose tissue in advancing tumor growth, we analyzed paired tumor-adjacent visceral adipose, normal mucosa, and colorectal tumor tissues as well as presurgery blood samples from patients with sporadic colorectal cancer. We report that high peroxisome proliferator-activated receptor gamma (PPARG) visceral adipose tissue expression is associated with glycoprotein VI (GPVI) signaling—the major signaling receptor for collagen—as well as fibrosis and adipogenesis pathway signaling in colorectal tumors. These associations were supported by correlations between PPARG visceral adipose tissue expression and circulating levels of plasma 4-hydroxyproline and serum intercellular adhesion molecule 1 (ICAM1), as well as gene set enrichment analysis and joint gene-metabolite pathway results integration that yielded significant enrichment of genes defining epithelial-to-mesenchymal transition—as in fibrosis and metastasis—and genes involved in glycolytic metabolism, confirmed this association. We also reveal that elevated prostaglandin-endoperoxide synthase 2 (PTGS2) colorectal tumor expression is associated with a fibrotic signature in adipose–tumor crosstalk via GPVI signaling and dendritic cell maturation in visceral adipose tissue. Systemic metabolite and biomarker profiling confirmed that high PTGS2 expression in colorectal tumors is significantly associated with higher concentrations of serum amyloid A and glycine, and lower concentrations of sphingomyelin, in patients with colorectal cancer. This multi-omics study suggests that adipose–tumor crosstalk in patients with colorectal cancer is a critical microenvironment interaction that could be therapeutically targeted. See related spotlight by Colacino et al., p. 803 |
| Databáze: | OpenAIRE |
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