S100A4: a common mediator of epithelial-mesenchymal transition, fibrosis and regeneration in diseases?

被引:150
作者
Schneider, Mikael [1 ,4 ]
Hansen, Jakob L. [2 ,3 ]
Sheikh, Soren P. [1 ,4 ]
机构
[1] Odense Univ Hosp, Dept Biochem Pharmacol & Genet, Lab Mol & Cellular Cardiol, DK-5000 Odense C, Denmark
[2] Univ Copenhagen Hosp, Mol Cardiol Lab, Danish Natl Res Fdn, Ctr Cardiac Arrhythmia,Heart Ctr,Rigshosp Sect 93, DK-2100 Copenhagen, Denmark
[3] Univ Copenhagen, Mol Pharmacol Lab, Dept Neurosci & Pharmacol, DK-2200 Copenhagen, Denmark
[4] Univ So Denmark, Inst Med Biol, DK-5000 Odense C, Denmark
来源
JOURNAL OF MOLECULAR MEDICINE-JMM | 2008年 / 86卷 / 05期
关键词
S100A4; fibroblast-specific protein 1; Fsp1; Mts1; fibrosis; epithelial-mesenchymal transition; EMT; remodelling; regeneration; cell motility; paracrine signalling;
D O I
10.1007/s00109-007-0301-3
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Multiple reports have focused on S100A4's role in cancer progression, specifically its ability to enhance metastasis. However, recent studies have linked S100A4 to several diseases besides cancer, including kidney fibrosis, cirrhosis, pulmonary disease, cardiac hypertrophy and fibrosis, arthritis and neuronal injuries. Common to all these diseases is the involvement of fibrotic and inflammatory processes, i.e. processes greatly dependent on tissue remodelling, cell motility and epithelial-mesenchymal transition. Therefore, the basic biological mechanisms behind S100A4's effects are emerging. S100A4 belongs to the S100 family of proteins that contain two Ca2+-binding sites including a canonical EF-hand motif. S100A4 is involved in the regulation of a wide range of biological effects including cell motility, survival, differentiation and contractility. S100A4 has both intracellular and extracellular effects. Hence, S100A4 interacts with cytoskeletal proteins and enhances metastasis of several types of cancer cells. In addition, S100A4 is secreted by unknown mechanisms, thus, paracrinely stimulating a variety of cellular responses, including angiogenesis and neuronal growth. Although many cellular effects of S100A4 are well described, the molecular mechanisms whereby S100A4 elicits these responses remain largely unknown. However, it is likely that the intracellular and the extracellular effects involve distinct mechanisms. In this review, we explore the possible roles of S100A4 in non-cancer diseases and employ this knowledge to describe underlying biological mechanisms including a change in cellular phenotype towards less tightly adherent cells and activation of fibrotic processes that may explain this protein's involvement in multiple pathologies.
引用
收藏
页码:507 / 522
页数:16
相关论文
共 131 条
[1]   Focal S100A4 protein expression is an independent predictor of development of metastatic disease in cystectomized bladder cancer patients [J].
Agerbaek, Mads ;
Aisner, Jan ;
Marcussen, Niels ;
Lundbeck, Finn ;
Von Der Maase, Hans .
EUROPEAN UROLOGY, 2006, 50 (04) :777-785
[2]   The metastasis-associated Mts1(S100A4) protein could act as an angiogenic factor [J].
Ambartsumian, N ;
Klingelhöfer, J ;
Grigorian, M ;
Christensen, C ;
Kriajevska, M ;
Tulchinsky, E ;
Georgiev, G ;
Berezin, V ;
Bock, E ;
Rygaard, J ;
Cao, RH ;
Cao, YH ;
Lukanidin, E .
ONCOGENE, 2001, 20 (34) :4685-4695
[3]  
Ambartsumian N, 1999, INVAS METAST, V18, P96
[4]  
Ambartsumian NS, 1996, ONCOGENE, V13, P1621
[5]   Transforming growth factor beta in cardiovascular development and function [J].
Azhar, M ;
Schultz, JEJ ;
Grupp, I ;
Dorn, GW ;
Meneton, P ;
Molin, DGM ;
Gittenberger-de Groot, AC ;
Doetschman, T .
CYTOKINE & GROWTH FACTOR REVIEWS, 2003, 14 (05) :391-407
[6]   Calcium-binding protein S100A4 in health and disease [J].
Barraclough, R .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 1998, 1448 (02) :190-199
[7]   Extracellular S100A4 stimulates the migration rate of astrocytic tumor cells by modifying the organization of their actin cytoskeleton [J].
Belot, N ;
Pochet, R ;
Heizmann, CW ;
Kiss, R ;
Decaestecker, C .
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, 2002, 1600 (1-2) :74-83
[8]   Intimal smooth muscle cells of porcine and human coronary artery express S100A4, a marker of the rhomboid phenotype in vitro [J].
Brisset, Anne C. ;
Hao, Hiroyuki ;
Camenzind, Edoardo ;
Bacchetta, Marc ;
Geinoz, Antoine ;
Sanchez, Jean-Charles ;
Chaponnier, Christine ;
Gabbiani, Giulio ;
Bochaton-Piallat, Marie-Luce .
CIRCULATION RESEARCH, 2007, 100 (07) :1055-1062
[9]   Renewal of FSP1: A marker of fibrogenesis on human renal biopsies [J].
Bruneval, P ;
Rossert, J ;
Bariety, J .
KIDNEY INTERNATIONAL, 2005, 68 (03) :1366-1367
[10]   Expression of S100A4 by, a variety of cell types present in the tumor microenvironment of human breast cancer [J].
Cabezon, Teresa ;
Celis, Julio E. ;
Skibshoj, Inge ;
Klingelhofer, Jorg ;
Grigorian, Mariam ;
Gromov, Pavel ;
Rank, Fritz ;
Myklebust, June Helen ;
Maelandsmo, Gunhild M. ;
Lukanidin, Eugene ;
Ambartsumian, Noona .
INTERNATIONAL JOURNAL OF CANCER, 2007, 121 (07) :1433-1444