TY - JOUR T1 - Bioregulation of Kallikrein-related Peptidases 6, 10 and 11 by the Kinin B<sub>1</sub> Receptor in Breast Cancer Cells JF - Anticancer Research JO - Anticancer Res SP - 6925 LP - 6938 VL - 34 IS - 12 AU - PAMELA EHRENFELD AU - LORELLA MANSO AU - MARÍA F. PAVICIC AU - CAROLA E. MATUS AU - CARLOS BORQUEZ AU - ALEJANDRO LIZAMA AU - JOSÉ SARMIENTO AU - MARÍA T. POBLETE AU - KANTI D. BHOOLA AU - ANUPAN NARAN AU - CARLOS D. FIGUEROA Y1 - 2014/12/01 UR - http://ar.iiarjournals.org/content/34/12/6925.abstract N2 - The sera of patients with breast cancer have higher levels of des[Arg9]bradykinin, a kinin B1 receptor (B1R) agonist, than that from healthy individuals. Stimulation of breast cancer cells with the analog Lys-des[Arg9]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. ER -