title: Regulation of colon cancer cell proliferation and migration by MD-2 activity.
abstract: Evidence suggests that signalling through lipopolysaccharide (LPS) has a significant role in the development of gastrointestinal malignancies. We previously demonstrated the critical role of myeloid differentiation (MD)-2, the essential co-receptor of LPS, for induction of cyclooxygenase (Cox)-2 in intestinal epithelial cells. Cyclooxigenase-2 was suggested to play a key role in colorectal cancer through the effects of prostaglandin (PG) E(2) generated. We, therefore, addressed the role of MD-2 in several parameters related to malignancy, namely cell proliferation and migration, using colon cancer cells (HT-29). We found that overexpression of MD-2 confers a significantly greater proliferation and migration capacity to these cells. MD-2-dependent proliferation and migration appeared independent of Cox-2 activity but was reduced by endothelial growth factor receptor (EGFR) neutralizing antibodies as well as by pharmacological inhibition of EGFR tyrosine phosphorylation. We propose that MD-2 overexpression contributes to tumour aggressiveness via a Cox-2-independent excessive EGFR signalling. Moreover, MD-2 expression levels were higher in tissue from patients with colorectal cancer as compared with paired control colorectal mucosa. Our data attest to a role of MD-2 activity in colon cancer epithelial cell proliferation and migration, which may be important in the general correlation between innate immune response, chronic inflammation, and cancer.
authors.affiliation: ER7-UPMC, University of Paris 6, Paris, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Grondin
authors.forename: Philippe
authors.initials: P
authors.lastname: Seksik
authors.forename: Sylvie
authors.initials: S
authors.lastname: Dumont
authors.forename: Ginette
authors.initials: G
authors.lastname: Thomas
authors.forename: Germain
authors.initials: G
authors.lastname: Trugnan
authors.forename: Jean François
authors.initials: JF
authors.lastname: Fléjou
authors.forename: Joelle
authors.initials: J
authors.lastname: Masliah
authors.forename: Dominique
authors.initials: D
authors.lastname: Wendum
authors.forename: Maria
authors.initials: M
authors.lastname: Bachelet
mesh_terms: D000328:Adult; D019138:Antibodies, Blocking / Q000494:pharmacology; D002277:Carcinoma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007113:Immunity, Innate; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism; D051218:Lymphocyte Antigen 96 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D040262:Receptors, Vascular Endothelial Growth Factor / Q000276:immunology / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics
chemical_list: D019138:Antibodies, Blocking; C495377:LY96 protein, human; D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D040262:Receptors, Vascular Endothelial Growth Factor