Increased expression of fascin, motility associated protein, in cell cultures derived from ovarian cancer and in borderline and carcinomatous ovarian tumors

被引:113
作者
Hu, W
McCrea, PD
Deavers, M
Kavanagh, JJ
Kudelka, AP
Verschraegen, CF
机构
[1] Univ Texas, MD Anderson Canc Ctr, Sect Gynecol & Med Therapeut, Houston, TX 77030 USA
[2] Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA
[3] Univ Texas, MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA
关键词
ovarian neoplasm; fascin; metastasis; actin-bundling protein;
D O I
10.1023/A:1026596609969
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Fascin bundles actin microfilaments within dynamic cellular structures such as microspikes, stress fibers and membrane ruffles. Fascin overexpression induces membrane protrusions and increased cell motility, and is highly expressed in various transformed cells, and in specialized normal cells including neuronal, endothelial and dendritic cells. In breast cancer, fascin expression correlates with high-grade tumors. To investigate whether fascin might be a predictor factor for ovarian cancer progression, eighteen cell cultures derived from ovarian cancer, and thirty four archival paraffin-embedded material of normal versus borderline and carcinomatous ovaries were stained by immunocytochemistry and immunohistochemistry with fascin Mab 55K-2. Overall expression of the fascin protein was found in 50% (9/18) of cell cultures derived from original samples of ovarian tumors. Expression of fascin protein was found in 67% (6/9) of cell cultures derived from patients diagnosed with stage IV disease, and 33% (3/9) of cell cultures from patients diagnosed with stage II/III. There was no clear relationship between fascin expression and histologic types, tumor grade, or DNA ploidy. However, 75% of cell cultures, which developed into a xenograft after intraperitoneal inoculation, showed fascin expression, while 86% of non-tumorigenic cell cultures did not show fascin expression. Expression of fascin in these established ovarian tumor cell cultures was significantly associated with the ability for these cells to grow intraperitoneally (P <0.05). Furthermore, fascin was never expressed in normal epithelial ovarian tissues, but was present in all pathologic ovaries. Both diffuse and focal patterns were observed in borderline ovarian tumors (67% and 33%), advanced primary ovarian cancer (67% and 33%) and metastatic ovarian cancer (89% and 11%). Therefore, our data suggest that fascin could serve as a prognostic factor for abnormal ovarian epithelial pathology and could be a novel target for the treatment of ovarian cancer.
引用
收藏
页码:83 / 88
页数:6
相关论文
共 22 条
[11]   EPSTEIN-BARR-VIRUS INFECTION INDUCES EXPRESSION IN B-LYMPHOCYTES OF A NOVEL GENE ENCODING AN EVOLUTIONARILY CONSERVED 55-KILODALTON ACTIN-BUNDLING PROTEIN [J].
MOSIALOS, G ;
YAMASHIRO, S ;
BAUGHMAN, RW ;
MATSUDAIRA, P ;
VARA, L ;
MATSUMURA, F ;
KIEFF, E ;
BIRKENBACH, M .
JOURNAL OF VIROLOGY, 1994, 68 (11) :7320-7328
[12]   ACTIN-BUNDLING PROTEINS [J].
OTTO, JJ .
CURRENT OPINION IN CELL BIOLOGY, 1994, 6 (01) :105-109
[13]   FOURIER-ANALYSIS OF CELL MOTILITY - CORRELATION OF MOTILITY WITH METASTATIC POTENTIAL [J].
PARTIN, AW ;
SCHOENIGER, JS ;
MOHLER, JL ;
COFFEY, DS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (04) :1254-1258
[14]  
Pinkus GS, 1997, AM J PATHOL, V150, P543
[15]   Estrogen receptor mediated inhibition of cancer cell invasion and motility: An overview [J].
Rochefort, H ;
Platet, N ;
Hayashido, Y ;
Derocq, D ;
Lucas, A ;
Cunat, S ;
Garcia, M .
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1998, 65 (1-6) :163-168
[16]  
Sun S, 1997, LAB INVEST, V76, P133
[17]   beta-catenin associates with the actin-bundling protein fascin in a noncadherin complex [J].
Tao, YS ;
Edwards, RA ;
Tubb, B ;
Wang, S ;
Bryan, J ;
McCrea, PD .
JOURNAL OF CELL BIOLOGY, 1996, 134 (05) :1271-1281
[18]  
VERSCHRAEGEN CF, 1999, P AM ASS CANC RES A, V3291, P499
[19]   β-catenin:: a key mediator of Wnt signaling [J].
Willert, K ;
Nusse, R .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 1998, 8 (01) :95-102
[20]   Fascin, an actin-bundling protein, induces membrane protrusions and increases cell motility of epithelial cells [J].
Yamashiro, S ;
Yamakita, Y ;
Ono, S ;
Matsumura, F .
MOLECULAR BIOLOGY OF THE CELL, 1998, 9 (05) :993-1006