This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nielsen, B. S. Articles by López-Otín, C. Search for Related Content PubMed PubMed Citation Articles by Nielsen, B. S. Articles by López-Otín, C.

Collagenase-3 Expression in Breast Myofibroblasts as a Molecular Marker of Transition of Ductal Carcinoma in Situ Lesions to Invasive Ductal Carcinomas¹

Finsen Laboratory [B. S. N., L. R. L., K. D.] and the Department of Pathology [F. R.], Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark; Departamento de Morfología y Biologia Celular [J. M. L.] and Departamento de Bioquímica y Biología Molecular [M. B., C. L-O.], Instituto Universitario de Oncología, Universidad de Oviedo, 33006 Oviedo, Spain; and Servicio de Cirugia, Hospital de Jove, 33290 Gijon, Spain [F. V.]

Collagenase-3 (matrix metalloproteinase 13; MMP-13), a protease originally identified in breast carcinoma, is characterized by a potent degrading activity against a wide spectrum of extracellular matrix proteins. The aims of this study were to localize and identify the MMP-13-expressing cells in invasive human breast carcinoma and to evaluate the role of MMP-13 in transition to invasive lesions by studying ductal carcinoma in situ (DCIS). We found expression of MMP-13 in stromal fibroblast-like cells in all 21 invasive ductal carcinomas studied and in 4 of 9 invasive lobular carcinomas. In most carcinomas, expression of MMP-13 was limited to small stromal foci in the tumor area. Combined in situ hybridization and immunohistochemistry showed coexpression of -smooth muscle actin immunoreactivity and MMP-13 mRNA in myofibroblasts. In contrast, cytokeratin-positive cancer cells, -smooth muscle actin-positive vascular smooth muscle cells, CD68-positive macrophages, and CD31-positive endothelial cells were all MMP-13 mRNA negative. In situ hybridization for MMP-13 in 17 DCIS lesions revealed expression in 10 cases. Immunohistochemical analysis of all DCIS cases identified microinvasion in 8 of the 17 lesions. Seven of the eight lesions with microinvasion were MMP-13 positive. Further analysis showed that MMP-13 expression was often associated with the microinvasive events. This particular expression pattern was unique for MMP-13 among other MMPs analyzed, including MMP-2, -11, and -14. We conclude that MMP-13 is primarily expressed by myofibroblasts in human breast carcinoma and that expression in DCIS lesions often is associated with microinvasive events. On the basis of these data, we propose that MMP-13 may play an essential role during transition of DCIS lesions to invasive ductal carcinomas.

This article has been cited by other articles:

				N. Rocks, G. Paulissen, F. Quesada-Calvo, C. Munaut, M.-L. A. Gonzalez, M. Gueders, J. Hacha, C. Gilles, J.-M. Foidart, A. Noel, et al. ADAMTS-1 Metalloproteinase Promotes Tumor Development through the Induction of a Stromal Reaction In vivo Cancer Res., November 15, 2008; 68(22): 9541 - 9550. [Abstract] [Full Text] [PDF]

				K. Almholt, A. Juncker-Jensen, O. D. Laerum, K. Dano, M. Johnsen, L. R. Lund, and J. Romer Metastasis is strongly reduced by the matrix metalloproteinase inhibitor Galardin in the MMTV-PymT transgenic breast cancer model Mol. Cancer Ther., September 1, 2008; 7(9): 2758 - 2767. [Abstract] [Full Text] [PDF]

				G. A. Alyahya, M. Kolko, J. U. Prause, B. S. Nielsen, J. Wang, and S. Heegaard Matrix Metalloproteinase-2 Is Expressed in Melanoma-Associated Spongiform Scleropathy Invest. Ophthalmol. Vis. Sci., July 1, 2008; 49(7): 2806 - 2811. [Abstract] [Full Text] [PDF]

				E. Huet, B. Vallee, D. Szul, F. Verrecchia, S. Mourah, J. V. Jester, T. Hoang-Xuan, S. Menashi, and E. E. Gabison Extracellular matrix metalloproteinase inducer/CD147 promotes myofibroblast differentiation by inducing {alpha}-smooth muscle actin expression and collagen gel contraction: implications in tissue remodeling FASEB J, April 1, 2008; 22(4): 1144 - 1154. [Abstract] [Full Text] [PDF]

				A. Rizki, V. M. Weaver, S.-Y. Lee, G. I. Rozenberg, K. Chin, C. A. Myers, J. L. Bascom, J. D. Mott, J. R. Semeiks, L. R. Grate, et al. A Human Breast Cell Model of Preinvasive to Invasive Transition Cancer Res., March 1, 2008; 68(5): 1378 - 1387. [Abstract] [Full Text] [PDF]

				T. X. Pedersen, C. J. Pennington, K. Almholt, I. J. Christensen, B. S. Nielsen, D. R. Edwards, J. Romer, K. Dano, and M. Johnsen Extracellular protease mRNAs are predominantly expressed in the stromal areas of microdissected mouse breast carcinomas Carcinogenesis, July 1, 2005; 26(7): 1233 - 1240. [Abstract] [Full Text] [PDF]

				M. EGEBLAD, L.E. LITTLEPAGE, and Z. WERB The Fibroblastic Coconspirator in Cancer Progression Cold Spring Harb Symp Quant Biol, January 1, 2005; 70(0): 383 - 388. [Abstract] [PDF]

				B. V. Offersen, B. S. Nielsen, G. Hoyer-Hansen, F. Rank, S. Hamilton-Dutoit, J. Overgaard, and P. A. Andreasen The Myofibroblast Is the Predominant Plasminogen Activator Inhibitor-1-Expressing Cell Type in Human Breast Carcinomas Am. J. Pathol., November 1, 2003; 163(5): 1887 - 1899. [Abstract] [Full Text] [PDF]