title: Targeting chemokine pathways in esophageal adenocarcinoma.
abstract: Esophageal adenocarcinoma (EAC) is one of the fastest growing malignancies in the US and needs newer therapeutic and diagnostic strategies. Chronic inflammation plays a role in the pathogenesis of EAC and contributes to the dysplastic conversion of normal esophageal epithelium to Barrett's esophagus and frank adenocarcinoma. Chemokines play important roles in mediating inflammation and recent evidence implicates these ligands and their receptors in the development and spread of various tumors. We demonstrated that the chemokines IL8, CXCL1 and CXCL3 are significantly overexpressed during esophageal carcinogenesis and accompanied by amplification and demethylation of the chr4q21 gene locus. We also demonstrated that IL8 levels can be detected in serum of patients with EAC and can serve as potential biomarkers. We now demonstrate that inhibition of IL8 receptor, CXCR2, leads to decreased invasiveness of esophageal adenocarcinoma derived cells without affecting cellular proliferation. Taken together, these studies reveal the important roles that chemokines play in development of esophageal cancer and demonstrate that these pathways can serve as potential therapeutic targets.
authors.affiliation: a Albert Einstein College of medicine ; Montefiore Medical Center ; Bronx , NY USA.
authors.forename: Makardhwaj S
authors.initials: MS
authors.lastname: Shrivastava
authors.forename: Zulfiqar
authors.initials: Z
authors.lastname: Hussain
authors.forename: Orsolya
authors.initials: O
authors.lastname: Giricz
authors.forename: Niraj
authors.initials: N
authors.lastname: Shenoy
authors.forename: Rahul
authors.initials: R
authors.lastname: Polineni
authors.forename: Anirban
authors.initials: A
authors.lastname: Maitra
authors.forename: Amit
authors.initials: A
authors.lastname: Verma
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D001471:Barrett Esophagus / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D054360:Chemokine CXCL1 / Q000378:metabolism*; D019743:Chemokines, CXC / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016209:Interleukin-8 / Q000097:blood / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D053700:Receptors, Interleukin-8 / Q000037:antagonists & inhibitors / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C499707:CXCL3 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D016209:Interleukin-8; D053700:Receptors, Interleukin-8; D023063:Receptors, Interleukin-8B
keywords: CXCR2; IL8; barrett's esophagus; chemokines; esophageal adenocarcinoma