title: Expression of most matrix metalloproteinase family members in breast cancer represents a tumor-induced host response.
abstract: Matrix metalloproteinase (MMP) family members have been associated with advanced-stage cancer and contribute to tumor progression, invasion, and metastasis as determined by inhibitor studies. In situ hybridization was performed to analyze the expression and localization of all known MMPs in a series of human breast cancer biopsy specimens. Most MMPs were localized to tumor stroma, and all MMPs had very distinct expression patterns. Matrilysin was expressed by morphologically normal epithelial ducts within tumors and in tissue from reduction mammoplasties, and by epithelial-derived tumor cells. Many family members, including stromelysin-3, gelatinase A, MT-MMP, interstitial collagenase, and stromelysin-1 were localized to fibroblasts of tumor stroma of invasive cancers but in quite distinct, and generally widespread, patterns. Gelatinase B, collagenase-3, and metalloelastase expression were more focal; gelatinase B was primarily localized to endothelial cells, collagenase-3 to isolated tumor cells, and metalloelastase to cytokeratin-negative, macrophage-like cells. The MMP inhibitor, TIMP-1, was expressed in both stromal and tumor components in most tumors, and neither stromelysin-2 nor neutrophil collagenase were detected in any of the tumors. These results indicate that there is very tight and complex regulation in the expression of MMP family members in breast cancer that generally represents a host response to the tumor and emphasize the need to further evaluate differential functions for MMP family members in breast tumor progression.
authors.affiliation: Department of Cell Biology, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Heppner
authors.forename: L M
authors.initials: LM
authors.lastname: Matrisian
authors.forename: R A
authors.initials: RA
authors.lastname: Jensen
authors.forename: W H
authors.initials: WH
authors.lastname: Rodgers
mesh_terms: D016375:Antisense Elements (Genetics); D001943:Breast Neoplasms / Q000737:chemistry* / Q000503:physiopathology; D002278:Carcinoma in Situ / Q000737:chemistry / Q000503:physiopathology; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000503:physiopathology; D004727:Endothelium / Q000737:chemistry; D004848:Epithelium / Q000737:chemistry; D005260:Female; D005347:Fibroblasts / Q000737:chemistry; D006801:Humans; D017403:In Situ Hybridization; D008666:Metalloendopeptidases / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D016375:Antisense Elements (Genetics); D012333:RNA, Messenger; D008666:Metalloendopeptidases