Downregulation of connective tissue growth factor by three-dimensional matrix enhances ovarian carcinoma cell invasion

被引:32
作者
Barbolina, Maria V. [1 ]
Adley, Brian P. [2 ]
Kelly, David L. [3 ]
Shepard, Jaclyn [1 ]
Fought, Angela J. [4 ]
Scholtens, Denise [4 ]
Penzes, Peter [5 ]
Shea, Lonnie D. [1 ,6 ]
Stack, M. Sharon [7 ]
机构
[1] Northwestern Univ, Dept Biol & Chem Engn, Chicago, IL 60611 USA
[2] Northwestern Univ, Dept Pathol, Chicago, IL 60611 USA
[3] Univ Nebraska Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE USA
[4] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA
[5] Northwestern Univ, Dept Physiol, Chicago, IL 60611 USA
[6] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA
[7] Univ Missouri, Columbia, MO USA
关键词
ovarian carcinoma; metastasis; invasion; adhesion; connective tissue growth factor; BREAST-CANCER CELLS; I COLLAGEN; MECHANICAL-STRESS; MESOTHELIAL CELLS; FACTOR EXPRESSION; CCN FAMILY; ADHESION; METALLOPROTEINASE; FIBROBLASTS; PROTEINS;
D O I
10.1002/ijc.24347
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Epithelial ovarian carcinoma (EOC) is a leading cause of death from gynecologic malignancies, due mainly to the prevalence of undetected metastatic disease. The process of cell invasion during intraperitoneal anchoring of metastatic lesions requires concerted regulation of many processes, including modulation of adhesion to the extracellular matrix and localized invasion. Exploratory cDNA microarray analysis of early response genes (altered after 4 hr of 3D collagen culture) coupled with confirmatory real-time reverse-transcriptase polymerase chain reaction, multiple 3D cell culture matrices, Western blot, immunostaining, adhesion, migration and invasion assays were used to identify modulators of adhesion pertinent to EOC progression and metastasis. cDNA microarray analysis indicated a dramatic downregulation of connective tissue growth factor (CTGF) in EOC cells placed in invasion-mimicking conditions (3D Type 1 collagen). Examination of human EOC specimens revealed that CTGF expression was absent in 46% of the tested samples (n = 41), but was present in 100% of normal ovarian epithelium samples (n = 7). Reduced CTGF expression occurs in many types of cells and may be a general phenomenon displayed by cells encountering a 3D environment. CTGF levels were inversely correlated with invasion such that downregulation of CTGF increased, while its upregulation reduced collagen invasion. Cells adhered preferentially to a surface comprised of both collagen I anti CTGF relative to either component alone using alpha 6/beta 1 and alpha 3 beta 1 integrins. Together these data suggest that downregulation of CTGF in EOC cells may be important for cell invasion through modulation of cell-matrix adhesion. (C) 2009 UICC
引用
收藏
页码:816 / 825
页数:10
相关论文
共 62 条
[11]   The CCN family: a new stimulus package [J].
Brigstock, DR .
JOURNAL OF ENDOCRINOLOGY, 2003, 178 (02) :169-175
[12]   Ovarian carcinoma spheroids disaggregate on type I collagen and invade live human mesothelial cell monolayers [J].
Burleson, KM ;
Hansen, LK ;
Skubitz, APN .
CLINICAL & EXPERIMENTAL METASTASIS, 2004, 21 (08) :685-697
[13]   Ovarian carcinoma ascites spheroids adhere to extracellular matrix components and mesothelial cell monolayers [J].
Burleson, KM ;
Casey, RC ;
Skubitz, KM ;
Pambuccian, SE ;
Oegema, TR ;
Skubitz, APN .
GYNECOLOGIC ONCOLOGY, 2004, 93 (01) :170-181
[14]   MEDICAL PROGRESS - CANCER OF THE OVARY [J].
CANNISTRA, SA .
NEW ENGLAND JOURNAL OF MEDICINE, 1993, 329 (21) :1550-1559
[15]   Identification and in silico characterization of a novel gene: TPA induced trans-membrane protein [J].
Chan, CY ;
Salabat, MR ;
Ding, XZ ;
Kelly, DL ;
Talamonti, MS ;
Bell, RH ;
Adrian, TE .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 329 (02) :755-764
[16]   Connective tissue growth factor and its role in lung adenocarcinoma invasion and metastasis [J].
Chang, CC ;
Shih, JY ;
Jeng, YM ;
Su, JL ;
Lin, BZ ;
Chen, ST ;
Chau, YP ;
Yang, PC ;
Kuo, ML .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2004, 96 (05) :364-375
[17]   Mechanical regulation of the Cyr61/CCN1 and CTGF/CCN2 proteins - Implications in mechanical stress-associated pathologies [J].
Chaqour, Brahim ;
Goppelt-Struebe, Margarete .
FEBS JOURNAL, 2006, 273 (16) :3639-3649
[18]   CTGF enhances the motility of breast cancer cells via an integrin-αvβ3-ERK1/2-dependent S100A4-upregulated pathway [J].
Chen, Pai-Sheng ;
Wang, Ming-Yang ;
Wu, Shin-Ni ;
Su, Jen-Liang ;
Hong, Chih-Chen ;
Chuang, Shuang-En ;
Chen, Min-Wei ;
Hua, Kuo-Tai ;
Wu, Yu-Ling ;
Cha, Shih-Ting ;
Babu, Munisamy Suresh ;
Chen, Chiung-Nien ;
Lee, Po-Huang ;
Chang, King-Jen ;
Kuo, Min-Liang .
JOURNAL OF CELL SCIENCE, 2007, 120 (12) :2053-2065
[19]  
CHOMCZYNSKI P, 1993, BIOTECHNIQUES, V15, P532
[20]   SINGLE-STEP METHOD OF RNA ISOLATION BY ACID GUANIDINIUM THIOCYANATE PHENOL CHLOROFORM EXTRACTION [J].
CHOMCZYNSKI, P ;
SACCHI, N .
ANALYTICAL BIOCHEMISTRY, 1987, 162 (01) :156-159