title: The impact of inflammatory lipid mediators on colon cancer-initiating cells.
abstract: The role of inflammatory lipid-mediators in tumor progression is well recognized in colorectal cancer; however, if this includes promotion of cancer-initiating cells remains unclear. We show that the inflammatory lipid-mediators leukotriene D4 and prostaglandin E2 increased the Aldehyde dehydrogenase (ALDH(+) ) population, the colony formation capacity, and tumor growth in a xenograft model of colon cancer. The ALDH(+) cells showed significant resistance to irradiation and 5-fluorouracil treatment that could be further augmented by these lipid-mediators, occurring in parallel with increased target gene expression. Our data emphasize a role for tumor microenvironment derived inflammatory lipid-mediators to favor cancer stem cells-like characteristics and thus promote tumor progression.
authors.affiliation: Division of Cell and Experimental Pathology, Department of Laboratory Medicine, Lund University, Clinical Research Center, Skåne University Hospital, Malmö, Sweden.
authors.forename: Kishan
authors.initials: K
authors.lastname: Bellamkonda
authors.affiliation: Division of Cell and Experimental Pathology, Department of Laboratory Medicine, Lund University, Clinical Research Center, Skåne University Hospital, Malmö, Sweden.
authors.forename: Wondossen
authors.initials: W
authors.lastname: Sime
authors.affiliation: Division of Cell and Experimental Pathology, Department of Laboratory Medicine, Lund University, Clinical Research Center, Skåne University Hospital, Malmö, Sweden. anita.sjolander@med.lu.se.
authors.forename: Anita
authors.initials: A
authors.lastname: Sjölander
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D015232:Dinoprostone / Q000235:genetics*; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D017998:Leukotriene D4 / Q000235:genetics*; D008055:Lipids / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D059016:Tumor Microenvironment / Q000187:drug effects / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D008055:Lipids; D017998:Leukotriene D4; D015232:Dinoprostone; D005472:Fluorouracil
keywords: ALDH; LTD4; PGE2; cancer-initiating cells; colon cancer