title: Bioregulation of kallikrein-related peptidases 6, 10 and 11 by the kinin B₁ receptor in breast cancer cells.
abstract: The sera of patients with breast cancer have higher levels of des[Arg(9)]bradykinin, a kinin B1 receptor (B1R) agonist, than that from healthy individuals. Stimulation of breast cancer cells with the analog Lys-des[Arg(9)]bradykinin causes release of metalloproteinases-2 and -9 and increases cell proliferation. We examined the possibility that breast cancer cells, in addition to B1R, express the kinin-forming protease true tissue kallikrein (KLK1) and the endogenous proteins termed kininogens from which kinins are enzymatically released. Furthermore, we investigated whether stimulation of breast cancer cells with a B1R agonist would modify the cellular levels of KLK6, KLK10 and KLK11, three kallikrein-related peptidases with a still poorly-understood biological role in breast cancer. We found that breast cancer cells expressed KLK1 and kininogens, and that stimulation of estrogen-sensitive breast cancer cells with the B1R agonist produced down-regulation of KLK10 (a protease associated with growth suppression) but up-regulation of KLK11 and KLK6 (peptidases related to increased cell proliferation and invasiveness, respectively). Furthermore, we showed that the B1R agonist acts as a functional stimulus for the secretion of KLK1 and KLK6, an event relevant for kinin production and cell invasion, respectively.
authors.affiliation: Institute of Anatomy, Histology and Pathology, Universidad Austral de Chile, Valdivia, Chile pamelaehrenfeld74@gmail.com.
authors.forename: Pamela
authors.initials: P
authors.lastname: Ehrenfeld
authors.affiliation: PathWest, Department of Tissue Pathology, QE2 Medical Centre, Hospital Avenue, Nedlands, WA, Australia.
authors.forename: Lorella
authors.initials: L
authors.lastname: Manso
authors.affiliation: Institute of Anatomy, Histology and Pathology, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: María F
authors.initials: MF
authors.lastname: Pavicic
authors.affiliation: Institute of Anatomy, Histology and Pathology, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Carola E
authors.initials: CE
authors.lastname: Matus
authors.affiliation: Institute of Anatomy, Histology and Pathology, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Carlos
authors.initials: C
authors.lastname: Borquez
authors.affiliation: Institute of Anatomy, Histology and Pathology, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Lizama
authors.affiliation: Institute of Physiology, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: José
authors.initials: J
authors.lastname: Sarmiento
authors.affiliation: Institute of Anatomy, Histology and Pathology, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: María T
authors.initials: MT
authors.lastname: Poblete
authors.affiliation: Institute of Anatomy, Histology and Pathology, Universidad Austral de Chile, Valdivia, Chile Lung Institute of Western Australia, Centre for Asthma, Allergy and Respiratory Research, The University of Western Australia, Nedlands, WA, Australia.
authors.forename: Kanti D
authors.initials: KD
authors.lastname: Bhoola
authors.affiliation: PathWest, Department of Tissue Pathology, QE2 Medical Centre, Hospital Avenue, Nedlands, WA, Australia.
authors.forename: Anupan
authors.initials: A
authors.lastname: Naran
authors.affiliation: Institute of Anatomy, Histology and Pathology, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Carlos D
authors.initials: CD
authors.lastname: Figueroa
mesh_terms: D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D001943:Breast Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007609:Kallidin / Q000031:analogs & derivatives / Q000494:pharmacology; D007610:Kallikreins / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D007704:Kininogens / Q000096:biosynthesis; D061986:MCF-7 Cells; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D034741:RNA, Small Interfering; D043783:Receptor, Bradykinin B1 / Q000819:agonists*; D012697:Serine Endopeptidases / Q000096:biosynthesis* / Q000097:blood; D020840:Tissue Kallikreins / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation
chemical_list: D007704:Kininogens; D034741:RNA, Small Interfering; D043783:Receptor, Bradykinin B1; C114880:trypsin-like serine protease; C024626:bradykinin, des-Arg(9)-; D007609:Kallidin; C052787:kallidin, des-Arg(10)-; C100936:KLK10 protein, human; C103551:KLK6 protein, human; D007610:Kallikreins; D012697:Serine Endopeptidases; D020840:Tissue Kallikreins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D001920:Bradykinin
keywords: Breast cancer; KLK10; KLK11; KLK6; estrogen; kallikrein-related peptidases; kinin B1 receptor; tissue kallikrein (KLK1)