Adrenomedullin expression in epithelial ovarian cancers and promotes HO8910 cell migration associated with upregulating integrin α5β1 and phosphorylating FAK and paxillin

Deng Boya, Zhang Siyang, Miao Yuan, Zhuang Han, Zhang Xiaoli, Wen Fang, Zhang, Zhang Yi

Description

Epithelial ovarian cancer (EOC) is one of the leading causes of cancer deaths in women worldwide. Adrenomedullin (AM) is a multifunctional peptide which presents in various kinds of tumors. Methods In this study, we characterized the expression and function of AM in epithelial ovarian cancer using immunohistochemistry staining. Exogenous AM and small interfering RNA (siRNA) specific for AM receptor CRLR were treated to EOC cell line HO8910. Wound healing assay and flow cytometry were used to measure the migration ability and expression of integrin α5 of HO8910 cells after above treatments. Western blot was used to examine the phosphorylation of FAK and paxillin. Results We found that patients with high AM expression showed a higher incidence of metastasis, larger residual size of tumors after cytoreduction and shorter disease-free and overall survival time. Exogenous AM induced ovarian cancer cell migration in time- and dose- dependent manners. AM upregulated the expression of integrin α5 and phosphorylation of FAK, paxillin as well. Conclusions Our results suggested that AM contributed to the progression of EOC and had additional roles in EOC cell migration by activating the integrin α5β1 signaling pathway. Therefore, we presumed that AM could be a potential molecular therapeutic target for ovarian carcinoma.

Sujets

• AM
• Carcinogenesis
• Progression
• Migration
• Fak
• Paxillin

Informations

• Publié par: biomed
• Publié le: 01 janvier 2012
• Nombre de lectures: 7
• Langue: English
• Poids de l'ouvrage: 3 Mo

Extrait

Denget al.Journal of Experimental & Clinical Cancer Research2012,31:19 http://www.jeccr.com/content/31/1/19

R E S E A R C HOpen Access Adrenomedullin expression in epithelial ovarian cancers and promotes HO8910 cell migration associated with upregulating integrina5b1 and phosphorylating FAK and paxillin 1 23 4 31* 1* Boya Deng , Siyang Zhang , Yuan Miao , Zhuang Han , Xiaoli Zhang , Fang Wenand Yi Zhang

Abstract Background:Epithelial ovarian cancer (EOC) is one of the leading causes of cancer deaths in women worldwide. Adrenomedullin (AM) is a multifunctional peptide which presents in various kinds of tumors. Methods:In this study, we characterized the expression and function of AM in epithelial ovarian cancer using immunohistochemistry staining. Exogenous AM and small interfering RNA (siRNA) specific for AM receptor CRLR were treated to EOC cell line HO8910. Wound healing assay and flow cytometry were used to measure the migration ability and expression of integrina5 of HO8910 cells after above treatments. Western blot was used to examine the phosphorylation of FAK and paxillin. Results:We found that patients with high AM expression showed a higher incidence of metastasis, larger residual size of tumors after cytoreduction and shorter diseasefree and overall survival time. Exogenous AM induced ovarian cancer cell migration in time and dose dependent manners. AM upregulated the expression of integrin a5 and phosphorylation of FAK, paxillin as well. Conclusions:Our results suggested that AM contributed to the progression of EOC and had additional roles in EOC cell migration by activating the integrina5b1 signaling pathway. Therefore, we presumed that AM could be a potential molecular therapeutic target for ovarian carcinoma. Keywords:Epithelial ovarian cancer, AM, Carcinogenesis, Progression, Migration, Integrinα5β1, FAK, Paxillin

Background Epithelial ovarian cancer (EOC) is the sixth most com mon cancer and the fifth leading cause of cancer mor tality in women worldwide [1]. This lethal gynecological malignancy is commonly diagnosed at a late stage due to the silent early stage and easily metastasis. Many advances took place in the pathological study and in understanding the mechanisms involved in EOC pro gression, details still need further investigations [2,3]. Therefore, this is an urgent need of more effective and new molecular targeted therapies for EOC.

* Correspondence: [e-mail]; [e-mail] 1 Department of Gynecology, The First Hospital of China Medical University, Shenyang 110001, China Full list of author information is available at the end of the article

Adrenomedullin (AM) is a 52aminoacid peptide first isolated from human pheochromocytoma [4]. It belongs to a family of peptides with calcitonin generelated pep tide (CGRP) and Amylin [5]. AM was identified as a major regulator of carcinogenesis and tumor progres sion, and autocrine loop of AM was targeted as new strategies against human cancers [68]. AM gene expres sion was proved to be associated with histological grade and poor prognosis of ovarian cancer [9]. The expres sion of its receptor calcitonin receptorlike receptor CRLR together with modulation factors RAMP2/ RAMP3 were also found in EOC tissues and OVCAR3 cells [10,11]. Our previous study had found that AM was autocrined in EOC cell line CAOV3 by bFGF sti mulation [12].Thus we supposed that AM may play an important role in EOC progression.

© 2012 Deng et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.