Human secreted proteins SLURP-1 and SLURP-2 control the growth of epithelial cancer cells via interactions with nicotinic acetylcholine receptors
| Autor: | E N, Lyukmanova, M L, Bychkov, G V, Sharonov, A V, Efremenko, M A, Shulepko, D S, Kulbatskii, Z O, Shenkarev, A V, Feofanov, D A, Dolgikh, M P, Kirpichnikov |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Dose-Response Relationship
Drug Tumor Cells Cultured Antigens Ly Humans Epithelial Cells Themed Section: Research Papers Receptors Nicotinic skin and connective tissue diseases GPI-Linked Proteins Urokinase-Type Plasminogen Activator Recombinant Proteins Adaptor Proteins Signal Transducing Cell Proliferation |
| Zdroj: | British journal of pharmacology. 175(11) |
| ISSN: | 1476-5381 |
| Popis: | BACKGROUND AND PURPOSE: Nicotinic acetylcholine receptors (nAChRs) are a promising target for development of new anticancer therapies. Here we have investigated the effects of the endogenous human proteins SLURP‐1 and SLURP‐2, antagonists of nAChRs, on human epithelial cancer cells. EXPERIMENTAL APPROACH: Growth of epithelial cancer cells (A431, SKBR3, MCF‐7, A549, HT‐29) exposed to SLURP‐1, SLURP‐2, mecamylamine, atropine, timolol and gefitinib was measured by the WST‐1 test. Expression levels of SLURP‐1, α7‐nAChR and EGF receptors and their distribution in cancer cells were studied by confocal microscopy and flow cytometry. Secretion of endogenous SLURP‐1 by A431 cells under treatment with recombinant SLURP‐1 was analysed by Western‐blotting. KEY RESULTS: SLURP‐1 and SLURP‐2 significantly inhibited growth of A431, SKBR3, MCF‐7 and HT‐29 cells at concentrations above 1 nM, to 40–70% of the control, in 24 h. Proliferation of A549 cells was inhibited only by SLURP‐1. The anti‐proliferative activity of SLURPs on A431 cells was associated with nAChRs, but not with β‐adrenoceptors or EGF receptors. Action of gefitinib and SLURPs was additive and resulted almost complete inhibition of A431 cell proliferation during 24 h. Exposure of A431 cells to recombinant SLURP‐1 down‐regulated α7‐nAChR expression and induced secretion of endogenous SLURP‐1 from intracellular depots, increasing its concentration in the extracellular media. CONCLUSIONS AND IMPLICATIONS: SLURPs inhibit growth of epithelial cancer cells in vitro and merit further investigation as potential agents for anticancer therapy. LINKED ARTICLES: This article is part of a themed section on Nicotinic Acetylcholine Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.11/issuetoc |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text