title: Integrins and haptoglobin: Molecules overexpressed in ovarian cancer.
abstract: Integrins are adhesion molecules whose expression is upregulated during different cellular processes such as adhesion, growth, proliferation, migration, survival and differentiation, all of which are involved in neoplastic development. Several reports have linked the overexpression of integrins with epithelial ovarian cancer (EOC). Furthermore, fucosylated haptoglobin (Hp) isoforms with antioxidant activity and synthesized primarily in the liver have also been associated with various types of cancer, including ovarian cancer. Here, we determined the level of expression of three integrin heterodimers (α5β1, α6β4, and αVβ3) and fucosyltated Hp in two different settings: cell cultures and biopsies from ovarian cancer patients. On the one hand, integrin heterodimers were analyzed in the ovarian cancer cell line (SKOV-3), two primary cultures (INCan017 and INCan019) and a tumor derived from INCan017 (T-017) by Western blot. Statistical analysis was performed using one-way ANOVA. The SKOV-3 cell line, INCan017 and INCan019 primary cultures, and the T-017 tumor showed increased expression patterns of the α5, αV, β1, β3, and β4 integrin subunits when compared with healthy ovary tissue. We then analyzed the expression pattern of the integrin subunits as well as the fucosylated Hp in biopsies from patients with different histotypes of EOC by immunofluorescence. α5β1 and α6β4 integrins were expressed by 90% of the samples, whereas 80% expressed the αVβ3 integrin. Furthermore, Hp, fucosylated or not, was present at high levels in most biopsies. In fact, there was a statistical correlation between the expression of integrins or Hp and the presence of the disease given that α5β1, α6β4, and αVβ3 integrins, Hp, fucosylated Hp and additional fucosylation state of proteins were highly expressed in biopsies of EOC histotypes when compared with healthy ovarian tissue. However, the statistical analysis showed no association of the presence of integrins, Hp or fucosylation with clinical or pathological characteristics of EOC patients. These results suggest that increased expression of these molecules and of the fucosylation modification are characteristics of the malignant process itself. Therefore, these molecules may be promising therapeutic targets in patients with this type of neoplasia.
authors.affiliation: Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, Delegación Gustavo A. Madero, México, DF 07360, Mexico. Electronic address: jcvillegas@cinvestav.mx.
authors.forename: Julio César
authors.initials: JC
authors.lastname: Villegas-Pineda
authors.affiliation: Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, Delegación Gustavo A. Madero, México, DF 07360, Mexico. Electronic address: olgaribay@hotmail.com.
authors.forename: Olga Lilia
authors.initials: OL
authors.lastname: Garibay-Cerdenares
authors.affiliation: Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, Delegación Gustavo A. Madero, México, DF 07360, Mexico. Electronic address: arturomvi@hotmail.com.
authors.forename: Verónica Ivonne
authors.initials: VI
authors.lastname: Hernández-Ramírez
authors.affiliation: Instituto Nacional de Cancerología, SSA, Av. San Fernando 22, Sección 16, Tlalpan, México, DF 14080, Mexico. Electronic address: dolores.gallardo@prodigy.net.mx.
authors.forename: Dolores
authors.initials: D
authors.lastname: Gallardo-Rincón
authors.affiliation: Instituto Nacional de Cancerología, SSA, Av. San Fernando 22, Sección 16, Tlalpan, México, DF 14080, Mexico. Electronic address: dcantude@gmail.com.
authors.forename: David
authors.initials: D
authors.lastname: Cantú de León
authors.affiliation: Instituto Nacional de Cancerología, SSA, Av. San Fernando 22, Sección 16, Tlalpan, México, DF 14080, Mexico. Electronic address: madeliapmg@yahoo.com.mx.
authors.forename: María Delia
authors.initials: MD
authors.lastname: Pérez-Montiel-Gómez
authors.affiliation: Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, Delegación Gustavo A. Madero, México, DF 07360, Mexico. Electronic address: ptr@cinvestav.mx.
authors.forename: Patricia
authors.initials: P
authors.lastname: Talamás-Rohana
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D005260:Female; D005455:Fluorescent Antibody Technique; D006242:Haptoglobins / Q000032:analysis / Q000096:biosynthesis*; D064593:Heterografts; D006801:Humans; D016023:Integrins / Q000032:analysis / Q000096:biosynthesis*; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism* / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D006242:Haptoglobins; D016023:Integrins
keywords: Fucosylation; Haptoglobin; Integrins; Ovarian cancer; α5β1; α6β4; αVβ3