Comparative analysis and clinical value of the expression of metalloproteases and their inhibitors by intratumor stromal fibroblasts and those at the invasive front of breast carcinomas

被引:54
作者
Del Casar, J. M. [1 ,2 ,3 ]
Gonzalez, L. O. [1 ,2 ,4 ]
Alvarez, E. [1 ]
Junquera, S. [2 ]
Marin, L. [2 ]
Gonzalez, L. [2 ]
Bongera, M. [2 ]
Vazquez, J. [2 ]
Vizoso, F. J. [1 ,2 ,3 ]
机构
[1] Inst Univ Oncol Principado Asturias, Oviedo, Spain
[2] Fdn Hosp Jove, Unidad Invest, Gijon 33920, Asturias, Spain
[3] Fdn Hosp Jove, Serv Cirugia Gen, Gijon 33920, Asturias, Spain
[4] Fdn Hosp Jove, Serv Anat Patol, Gijon 33920, Asturias, Spain
关键词
Peritumor stroma; MMP; TIMP; Fibroblast; Tumor heterogeneity; MATRIX METALLOPROTEINASES; TUMOR-STROMA; TISSUE INHIBITORS; CANCER; CELLS; GROWTH; ANGIOGENESIS; MATRILYSIN; SIGNATURE; SURVIVAL;
D O I
10.1007/s10549-009-0351-z
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
An immunohistochemical study was performed using tissue arrays and specific antibodies against MMPs -1, -2, -7, -9, -11, -13, -14, and TIMPs -1, -2 and -3. More than 5,000 determinations on cancer specimens from 124 patients with invasive breast cancer were performed at the center of the tumor and the invasive front. Immunostaining for MMPs/TIMPs by fibroblasts was evaluated. To identify specific groups of tumors with distinct expression profiles, the data obtained from both fibroblast populations were analyzed by unsupervised hierarchical cluster analysis. Intratumor stromal fibroblasts more frequently showed expression of MMP-2, -7, and -14, and TIMP-3, but less frequently of MMP-9 than fibroblasts at the invasive front. Multivariate analysis showed that a high profile of MMPs and TIMPs staining in both fibroblast populations was the most potent predictor factor of distant metastases, whereas a low staining profile in fibroblasts was associated with a low risk of metastases.
引用
收藏
页码:39 / 52
页数:14
相关论文
共 36 条
[1]
A Mouse Stromal Response to Tumor Invasion Predicts Prostate and Breast Cancer Patient Survival [J].
Bacac, Marina ;
Provero, Paolo ;
Mayran, Nathalie ;
Stehle, Jean-Christophe ;
Fusco, Carlo ;
Stamenkovic, Ivan .
PLOS ONE, 2006, 1 (01)
[2]
The fibromatosis signature defines a robust stromal response in breast carcinoma [J].
Beck, Andrew H. ;
Espinosa, Inigo ;
Gilks, C. Blake ;
van de Rijn, Matt ;
West, Robert B. .
LABORATORY INVESTIGATION, 2008, 88 (06) :591-601
[3]
The Ets-1 transcription factor is up-regulated together with MMP 1 and MMP 9 in the stroma of pre-invasive breast cancer [J].
Behrens, P ;
Rothe, M ;
Wellmann, A ;
Krischler, J ;
Wernert, N .
JOURNAL OF PATHOLOGY, 2001, 194 (01) :43-50
[4]
Extracellular matrix signature identifies breast cancer subgroups with different clinical outcome [J].
Bergamaschi, A. ;
Tagliabue, E. ;
Sorlie, T. ;
Naurne, B. ;
Triulzi, T. ;
Orlandi, R. ;
Russnes, H. G. ;
Nesland, J. M. ;
Tammi, R. ;
Auvinen, P. ;
Kosma, V-M ;
Menard, S. ;
Borresen-Dale, A-L .
JOURNAL OF PATHOLOGY, 2008, 214 (03) :357-367
[5]
Tumor-stroma interactions [J].
Bhowmick, NA ;
Moses, HL .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 2005, 15 (01) :97-101
[6]
Robustness, scalability, and integration of a wound-response gene expression signature in predicting breast cancer survival [J].
Chang, HY ;
Nuyten, DSA ;
Sneddon, JB ;
Hastie, T ;
Tibshirani, R ;
Sorlie, T ;
Dai, HY ;
He, YDD ;
van't Veer, LJ ;
Bartelink, H ;
van de Rijn, M ;
Brown, PO ;
van de Vijver, MJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (10) :3738-3743
[7]
Cornelius LA, 1998, J IMMUNOL, V161, P6845
[8]
New functions for the matrix metalloproteinases in cancer progression [J].
Egeblad, M ;
Werb, Z .
NATURE REVIEWS CANCER, 2002, 2 (03) :161-174
[9]
Cluster analysis and display of genome-wide expression patterns [J].
Eisen, MB ;
Spellman, PT ;
Brown, PO ;
Botstein, D .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (25) :14863-14868
[10]
Stromal gene expression predicts clinical outcome in breast cancer [J].
Finak, Greg ;
Bertos, Nicholas ;
Pepin, Francois ;
Sadekova, Svetlana ;
Souleimanova, Margarita ;
Zhao, Hong ;
Chen, Haiying ;
Omeroglu, Gulbeyaz ;
Meterissian, Sarkis ;
Omeroglu, Atilla ;
Hallett, Michael ;
Park, Morag .
NATURE MEDICINE, 2008, 14 (05) :518-527