Villegas-Pineda Julio César, Garibay-Cerdenares Olga Lilia, Hernández-Ramírez Verónica Ivonne, Gallardo-Rincón Dolores, Cantú de León David, Pérez-Montiel-Gómez María Delia, Talamás-Rohana Patricia
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.
Instituto Nacional de Cancerología, SSA, Av. San Fernando 22, Sección 16, Tlalpan, México, DF 14080, Mexico.
Pathol Res Pract. 2015 Dec;211(12):973-81. doi: 10.1016/j.prp.2015.10.002. Epub 2015 Nov 6.
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.
整合素是一类黏附分子，其表达在不同的细胞过程中上调，如黏附、生长、增殖、迁移、存活和分化，所有这些过程都与肿瘤发生发展有关。多项报告将整合素的过表达与上皮性卵巢癌（EOC）联系起来。此外，主要在肝脏中合成的具有抗氧化活性的岩藻糖基化触珠蛋白（Hp）同工型也与包括卵巢癌在内的多种癌症相关。在此，我们在两种不同情况下测定了三种整合素异二聚体（α5β1、α6β4和αVβ3）以及岩藻糖基化Hp的表达水平：卵巢癌细胞培养物和卵巢癌患者的活检组织。一方面，通过蛋白质印迹法分析了卵巢癌细胞系（SKOV - 3）、两种原代培养物（INCan017和INCan019）以及源自INCan017的肿瘤（T - 017）中的整合素异二聚体。使用单因素方差分析进行统计分析。与健康卵巢组织相比，SKOV - 3细胞系、INCan017和INCan019原代培养物以及T - 017肿瘤显示出α5、αV、β1、β3和β4整合素亚基的表达模式增加。然后，我们通过免疫荧光分析了不同组织学类型的EOC患者活检组织中整合素亚基以及岩藻糖基化Hp的表达模式。90%的样本表达α5β1和α6β4整合素，而80%的样本表达αVβ3整合素。此外，无论是否岩藻糖基化，Hp在大多数活检组织中都高水平存在。事实上，整合素或Hp的表达与疾病的存在之间存在统计学相关性，因为与健康卵巢组织相比，α5β1、α6β4和αVβ3整合素、Hp、岩藻糖基化Hp以及蛋白质的其他岩藻糖基化状态在EOC组织学类型的活检组织中高表达。然而，统计分析表明整合素、Hp或岩藻糖基化的存在与EOC患者的临床或病理特征无关。这些结果表明，这些分子的表达增加以及岩藻糖基化修饰是恶性过程本身的特征。因此，这些分子可能是这类肿瘤患者有前景的治疗靶点。
