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.
|Publication status||Published - 2014|
Ehrenfeld, P., Manso, L., Pavicic, M. F., Matus, C. E., Bórquez, C., Lizama, A., Sarmiento, J. M., Poblete, M. T., Bhoola, K., Naran, A., & Figueroa, C. D. (2014). Bioregulation of kallikrein-related peptidases 6, 10 and 11 by the Kinin b1 receptor in breast cancer cells. Anticancer Research, 34(12), 6925-6938.