Bioregulation of kallikrein-related peptidases 6, 10 and 11 by the Kinin b1 receptor in breast cancer cells

P. Ehrenfeld, L. Manso, M.F. Pavicic, C.E. Matus, C. Bórquez, A. Lizama, J.M. Sarmiento, M.T. Poblete, Kanti Bhoola, A. Naran, C.D. Figueroa

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    11 Citations (Scopus)

    Abstract

    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.
    Original languageEnglish
    Pages (from-to)6925-6938
    JournalAnticancer Research
    Volume34
    Issue number12
    Publication statusPublished - 2014

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  • Cite this

    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.