title: Influence of GRPR and BDNF/TrkB signaling on the viability of breast and gynecologic cancer cells.
abstract: Neuropeptide and neurotrophin receptors are increasingly important molecular targets in cancer. Scientific findings indicate that compounds blocking gastrin-releasing peptide receptors (GRPR) or tropomyosin receptor kinase (Trk) receptors are likely to have antiproliferative activities against cancer cells. The present study aimed to demonstrate that, in contrast to previous findings, GRPR activation reduces, whereas its blockade increases the viability of breast, ovarian and cervical cancer cell lines. However, consistent with previous studies, Trk inhibition was demonstrated to reduce the viability of these cells. MCF-7 (breast), OVCAR-3 (ovarian) and HeLa (cervical) human cancer cell lines were treated with GRP, the GRPR antagonists RC-3095 and RC-3940-II, brain-derived neurotrophic factor (BDNF) and the Trk antagonist K252α. Cell viability was measured by the MTT assay. Expression of GRPR and BDNF was confirmed with reverse transcription-polymerase chain reaction (RT-PCR). GRP reduced, whereas RC-3940-II enhanced the viability of the three cell lines. Treatment with K252α inhibited the viability of the cell lines, while BDNF increased the viability of OVCAR-3 cells. The results supported the hypothesis that GRPR and BDNF/TrkB signaling regulates cancer cell viability. Most importantly, these findings are the first to demonstrate that GRPR blockade can stimulate, rather than inhibits the viability of breast and gynecologic cancer cell lines.
authors.affiliation: Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA);
authors.forename: Daniela B
authors.initials: DB
authors.lastname: Cornelio
authors.affiliation: Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA);
authors.forename: Caroline B
authors.initials: CB
authors.lastname: DE Farias
authors.affiliation: Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA);
authors.forename: Débora S
authors.initials: DS
authors.lastname: Prusch
authors.affiliation: Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA);
authors.forename: Tiago E
authors.initials: TE
authors.lastname: Heinen
authors.affiliation: Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA);
authors.forename: Rafael P
authors.initials: RP
authors.lastname: Dos Santos
authors.affiliation: Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA);
authors.forename: Ana L
authors.initials: AL
authors.lastname: Abujamra
authors.affiliation: Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA); ; National Institute for Translational Medicine (INCT-TM); ; Department of Internal Medicine, School of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Schwartsmann
authors.affiliation: Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA);
authors.forename: Rafael
authors.initials: R
authors.lastname: Roesler
keywords: brain-derived neurotrophic factor; cancer cell; gastrin-releasing peptide receptor; gynecologic cancer; tropomyosin receptor kinase B