title: Human breast cancer-associated fibroblasts enhance cancer cell proliferation through increased TGF-α cleavage by ADAM17.
abstract: We demonstrate here increased expression of ADAM17 protein in cancer-associated fibroblasts (CAFs) extracted from human breast carcinomas compared with donor-matched normal fibroblasts, and TGF-α secretion positively correlates with ADAM17 expression in these cells. In SK-BR-3 cells co-cultured with CAFs, CAF-secreted TGF-α promotes cell proliferation by activation of EGFR, Akt, and ERK, but it does not promote cell migration. Furthermore, anti-TGF-α neutralizing antibodies antagonize the CAF-dependent increase in proliferation and activation of EGFR, Akt and ERK. Thus, pharmacologic inhibition of ADAM17 and TGF-α may have therapeutic potential for the treatment of breast cancer when fibroblast-directed therapy is considered.
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul 120-752, South Korea.
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Gao
authors.forename: Baek Gil
authors.initials: BG
authors.lastname: Kim
authors.forename: Suki
authors.initials: S
authors.lastname: Kang
authors.forename: Yoon Pyo
authors.initials: YP
authors.lastname: Choi
authors.forename: Joo-Heon
authors.initials: JH
authors.lastname: Yoon
authors.forename: Nam Hoon
authors.initials: NH
authors.lastname: Cho
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000072198:ADAM17 Protein; D001940:Breast / Q000166:cytology; D001943:Breast Neoplasms / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D002633:Chemotaxis; D018450:Disease Progression; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D016211:Transforming Growth Factor alpha / Q000378:metabolism*
chemical_list: D016211:Transforming Growth Factor alpha; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human