title: Tumor tissue inhibitor of metalloproteinases-1 (TIMP-1) in hormone-independent breast cancer might originate in stromal cells, and improves stratification of prognosis together with nodal status.
abstract: Tissue inhibitor of metalloproteinases-1 (TIMP-1) is shown to be a potential marker for poor prognosis in breast cancer, but the biology of TIMP-1 is only partially understood. In this study, TIMP-1 production was studied in a co-culture model of hormone-independent breast cancer cell lines and mesenchymal stem cells mimicking the stromal components of the tumor. In addition, the prognostic value of TIMP-1 was histologically evaluated in a clinical material of 168 patients with hormone-independent breast tumors. The hormone-independent breast cancer (BC) cell lines MDA-MB-231, M4A4 and NM2C5 did not produce TIMP-1 protein in measureable quantities. Six tested primary mesenchymal stem cell lines all produced TIMP-1. Co-culturing of mesenchymal stem cells and breast cancer cells resulted in positive immunocytochemical diffuse staining for TIMP-1 for both cell types. Culturing breast cancer cells with MSC-conditioned media resulted in a positive cytoplasmic immunoreactivity for TIMP-1, and TIMP-1 protein concentration in cell lysates increased 2.7-fold (range 1.1-4.7). The TIMP-1 mRNA levels remained unaffected in BC cells. This might suggest that breast cancer cells can take up TIMP-1 produced by stromal cells and are thus displaying cellular immunoreactivity. In addition, TIMP-1 was shown to improve stratification of prognosis in clinical material.
authors.affiliation: Department of Oncology and Radiotherapy, Institute of Clinical Medicine, Oulu University Hospital, Oulu, Finland. paula.kuvaja@oulu.fi
authors.forename: P
authors.initials: P
authors.lastname: Kuvaja
authors.forename: S
authors.initials: S
authors.lastname: Hulkkonen
authors.forename: I
authors.initials: I
authors.lastname: Pasanen
authors.forename: Y
authors.initials: Y
authors.lastname: Soini
authors.forename: S
authors.initials: S
authors.lastname: Lehtonen
authors.forename: A
authors.initials: A
authors.lastname: Talvensaari-Mattila
authors.forename: P
authors.initials: P
authors.lastname: Pääkkö
authors.forename: M
authors.initials: M
authors.lastname: Kaakinen
authors.forename: H
authors.initials: H
authors.lastname: Autio-Harmainen
authors.forename: T
authors.initials: T
authors.lastname: Hurskainen
authors.forename: P
authors.initials: P
authors.lastname: Lehenkari
authors.forename: T
authors.initials: T
authors.lastname: Turpeenniemi-Hujanen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018275:Carcinoma, Lobular / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D011379:Prognosis; D011987:Receptors, Steroid / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D014408:Biomarkers, Tumor; D017077:Culture Media, Conditioned; D011987:Receptors, Steroid; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1