Human desmoid fibroblasts: matrix metalloproteinases, their inhibitors and modulation by Toremifene.
BACKGROUND
Desmoid tumour is a benign, non metastasising neoplasm characterised by an elevated deposition of organic macromolecules in the extracellular matrix (ECM). The matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases involved in the degradation of ECM macromolecules. The MMPs and their natural inhibitors (TIMPs) have been implicated in tumour growth, invasion and metastasis. In this study we provide evidence that the in vitro cultured cell line from desmoid tumour accumulates more collagen fibres in the ECM than healthy fibroblasts.


METHODS
We investigated collagen accumulation by 3H-thymidine incorporation, MMP expression by substrate gel zymography and TIMP expression by Western blot analysis.


RESULTS
Desmoid fibroblasts showed a reduction in MMP activity and an increase of type I and III collagen and TIMPs compared to normal fibroblasts.


CONCLUSIONS
The increase in collagen in desmoid fibroblasts was due to inhibited collagen degradation (reduction of MMP activity) rather than to increased collagen synthesis. Adding toremifene, an anti-estrogen triphenylethylene derivate, to desmoid fibroblasts reduced collagen accumulation by decreasing mRNA expression and increasing collagen degradation.
Balducci
Chiara
C
Department of Experimental Medicine and Biochemical Science, University of Perugia, Perugia, Italy. chiara.balducci@tiscali.it <chiara.balducci@tiscali.it>
Lilli
Cinzia
C
Stabellini
Giordano
G
Marinucci
Lorella
L
Giustozzi
Giammario
G
Becchetti
Alessio
A
Cagini
Lucio
L
Locci
Paola
P
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D045744:Cell Line, Tumor; D003094:Collagen / Q000032:analysis*; D017364:Collagenases / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology*; D018222:Desmoid Tumors / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000187:drug effects / Q000378:metabolism*; D011347:Procollagen / Q000032:analysis; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D017312:Toremifene / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D018931:Antineoplastic Agents, Hormonal; D061965:Matrix Metalloproteinase Inhibitors; D011347:Procollagen; D019714:Tissue Inhibitor of Metalloproteinases; D017312:Toremifene; D003094:Collagen; D017364:Collagenases; D020782:Matrix Metalloproteinases
Cancer Lett. 2003 Oct 8;200(1):49-55
14550952
Gut. 1998 Dec;43(6):791-7
9824606
J Interferon Cytokine Res. 2001 Nov;21(11):961-70
11747628
Am J Hum Genet. 1996 Dec;59(6):1193-201
8940264
Curr Opin Cell Biol. 1998 Oct;10(5):602-8
9818170
Biol Reprod. 2003 Apr;68(4):1276-81
12606436
J Biol Chem. 2003 Oct 10;278(41):40364-72
12904305
Int J Cancer. 2002 Apr 20;98(6):824-32
11948458
Pathol Int. 1998 Aug;48(8):603-10
9736407
J Periodontol. 2002 Nov;73(11):1313-22
12479636
Nature. 1970 Aug 15;227(5259):680-5
5432063
Crit Rev Oral Biol Med. 1993;4(2):197-250
8435466
Anal Biochem. 1979 Jul 1;96(1):220-4
495986
Clin Cancer Res. 2001 Aug;7(8):2396-404
11489818
Cytokine. 1998 May;10(5):353-60
9619373
Curr Med Chem. 2001 Mar;8(4):425-74
11172697
Int J Cancer. 2001 Aug 15;93(4):507-15
11477554
Cancer. 1998 Apr 1;82(7):1359-66
9529029
Mol Cell Biochem. 1999 Apr;194(1-2):99-108
10391129
Ann Surg. 1999 Jun;229(6):866-72; discussion 872-3
10363901
Biochem Biophys Res Commun. 1999 Aug 11;261(3):904-10
10441523
Am J Physiol. 1999 May;276(5):L814-24
10330038
Int J Dev Biol. 1999 Mar;43(2):157-65
10235392
Ann Med. 1999 Feb;31(1):34-45
10219712
Eur J Cancer. 1992;28A(6-7):1014-8
1385717
Biochem J. 2003 Sep 15;374(Pt 3):739-45
12755684
Aust N Z J Surg. 1996 Jul;66(7):457-63
8678875
Anal Biochem. 1998 Jan 15;255(2):211-6
9451506
J Biol Chem. 1995 Mar 17;270(11):5872-6
7890717
J Natl Cancer Inst. 2002 Jan 2;94(1):17-25
11773278
Eur J Cell Biol. 1997 Oct;74(2):111-22
9352216
J Biol Chem. 1951 Nov;193(1):265-75
14907713
Cell. 2000 Oct 13;103(2):295-309
11057902
J Cell Physiol. 2001 Jan;186(1):53-64
11147814
Curr Opin Cell Biol. 1998 Oct;10(5):667-71
9818179
Anal Biochem. 1987 Apr;162(1):156-9
2440339