title: Monoclonal antibody 14C5 targets integrin alphavbeta5.
abstract: This study identifies and characterizes the antigen recognized by monoclonal antibody (mAb) 14C5. We compared the expression of antigen 14C5 with the expression of eight integrin subunits (alpha1, alpha2, alpha3, alphav, beta1, beta2, beta3, and beta4) and three integrin heterodimers (alphavbeta3, alphavbeta5, and alpha5beta1) by flow cytometry. Antigen 14C5 showed a similar expression to alphavbeta5 in eight different epithelial cancer cell lines (A549, A2058, C32, Capan-2, Colo16, HT-1080, HT-29, and SKBR-3). Specific binding of P1F6, an anti-alphavbeta5 specific antibody, was blocked by mAb 14C5. After transient expression of alphavbeta5 in 14C5-negative Colo16 cells, mAb 14C5 was able to bind a subpopulation of alphavbeta5-positive cells. We evaluated the tissue distribution of the 14C5 antigen in colon (n = 20) and lung (n = 16) cancer tissues. The colon carcinoma cells stained positive for 14C5 in 50% of tumors analyzed, whereas bronchoalveolar lung carcinoma and typical carcinoid were not positive for the antigen. More common types of non-small cell lung cancer, i.e., squamous (n = 5) and adenocarcinoma (n = 3), stained positive in 2 of 5 squamous carcinomas and in 1 of 3 investigated adenocarcinoma. Colon (95%) and lung (50%) carcinoma tissues showed extensive expression of antigen 14C5 in the stroma surrounding the tumor cells and on the membrane of the adjacent fibroblasts. We show for the first time that mAb 14C5 binds the vascular integrin alphavbeta5, suggesting that mAb 14C5 can be used as a screening agent to select colon and lung cancer patients that are eligible for anti-alphavbeta5-based therapies.
authors.affiliation: Laboratory of Radiopharmacy, Harelbekestraat 72, B-9000 Ghent, Belgium.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Burvenich
authors.forename: Steve
authors.initials: S
authors.lastname: Schoonooghe
authors.forename: Liesbet
authors.initials: L
authors.lastname: Vervoort
authors.forename: Caroline
authors.initials: C
authors.lastname: Dumolyn
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Coene
authors.forename: Lieve
authors.initials: L
authors.lastname: Vanwalleghem
authors.forename: Jacques
authors.initials: J
authors.lastname: Van Huysse
authors.forename: Marleen
authors.initials: M
authors.lastname: Praet
authors.forename: Claude
authors.initials: C
authors.lastname: Cuvelier
authors.forename: Nico
authors.initials: N
authors.lastname: Mertens
authors.forename: Filip
authors.initials: F
authors.lastname: De Vos
authors.forename: Guido
authors.initials: G
authors.lastname: Slegers
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000502:physiology*; D000951:Antigens, Neoplasm / Q000737:chemistry; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D005434:Flow Cytometry / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011485:Protein Binding; D019030:Receptors, Vitronectin / Q000378:metabolism / Q000502:physiology*; D014018:Tissue Distribution
chemical_list: C488070:14C5 monoclonal antibody; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5