title: Inhibitory effects of anti-CXCR4 antibodies on human colon cancer cells.
abstract: BACKGROUND
  CXCR4, the chemokine receptor for CXCL12, has recently been involved in the metastatic process of several neoplasms.
  
  
  METHODS
  The expression of CXCR4 was evaluated by immunohistochemistry of colorectal tissue samples and by flow cytometry on Caco2, GEO, SW480, SW48, Lovo and SW620 human colon carcinoma cell lines. Correlations with pathological characteristics of the specimens were analysed with chi-square test. To verify the functional status of CXCR4, cell lines were tested in adhesion, migration, and proliferation assays.
  
  
  RESULTS
  We studied the expression of CXCR4 in 88 human colorectal tissues and we found that CXCR4 was expressed in > 10% of epithelial cells in 50% of normal mucosae (7/14), in 55% of polyps (29/53), in all of carcinomas (16/16) and hepatic metastasis (5/5). Notably, CXCR4 was significantly over-expressed in cancerous lesions (carcinomas and metastasis) compared to non-cancerous lesions (normal mucosa and polyps) (P = 0.003) and in adenomatous polyps versus hyperplastic polyps (P = 0.009). The diameter of a polyp was also significantly associated with CXCR4 expression (P = 0.031). SW480, SW48 and SW620 cell lines showed the highest levels of CXCR4 (60-80% of positive cells). Adhesion, migration, and proliferation increased in response to the CXCL12 chemokine. These effects were abrogated by the addition of anti-CXCR4 antibodies. Further, CXCL12 activated ERK1/2 in SW480 cells.
  
  
  CONCLUSIONS
  These data suggest that CXCR4 might play a role in colon cancer cell properties and that anti-CXCR4 antibodies could have therapeutic effects against colorectal cancer.
authors.affiliation: Division of Clinical Immunology, National Cancer Institute, via M. Semmola, 80131 Naples, Italy. ale.otto@libero.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ottaiano
authors.forename: Antonella
authors.initials: A
authors.lastname: di Palma
authors.forename: Maria
authors.initials: M
authors.lastname: Napolitano
authors.forename: Carmen
authors.initials: C
authors.lastname: Pisano
authors.forename: Sandro
authors.initials: S
authors.lastname: Pignata
authors.forename: Fabiana
authors.initials: F
authors.lastname: Tatangelo
authors.forename: Gerardo
authors.initials: G
authors.lastname: Botti
authors.forename: Angela Maria
authors.initials: AM
authors.lastname: Acquaviva
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Castello
authors.forename: Paolo Antonio
authors.initials: PA
authors.lastname: Ascierto
authors.forename: Rosario Vincenzo
authors.initials: RV
authors.lastname: Iaffaioli
authors.forename: Stefania
authors.initials: S
authors.lastname: Scala
mesh_terms: D000906:Antibodies / Q000276:immunology; D018938:Caco-2 Cells; D002277:Carcinoma / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D002633:Chemotaxis / Q000276:immunology; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000556:secondary; D009362:Neoplasm Metastasis / Q000276:immunology*; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000276:immunology*
chemical_list: D000906:Antibodies; D019718:Receptors, CXCR4