Bioregulation of Kallikrein-related Peptidases 6, 10 and 11 by the Kinin B-1 Receptor in Breast Cancer Cells

Ehrenfeld, P; Manso, L; Pavicic, MF; Matus, CE; Borquez, C; Lizama A.; Sarmiento J.; Poblete, MT; Bhoola, KD; Naran, A; Figueroa, CD

Keywords: estrogen, breast cancer, kinin B-1 receptor, tissue kallikrein (KLK1), kallikrein-related peptidases, KLK6, KLK10, KLK11

Abstract

The sera of patients with breast cancer have higher levels of des[Arg(9)]bradykinin, a kinin B-1 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.

Más información

Título según WOS: Bioregulation of Kallikrein-related Peptidases 6, 10 and 11 by the Kinin B-1 Receptor in Breast Cancer Cells
Título de la Revista: Anticancer research.
Volumen: 34
Número: 12
Editorial: INT INST ANTICANCER RESEARCH
Fecha de publicación: 2014
Página de inicio: 6925
Página final: 6938
Idioma: English
Notas: ISI