Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular and Clinical Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 2049-9450 Online ISSN: 2049-9469
Journal Cover
January-February 2013 Volume 1 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
January-February 2013 Volume 1 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Influence of GRPR and BDNF/TrkB signaling on the viability of breast and gynecologic cancer cells

  • Authors:
    • Daniela B. Cornelio
    • Caroline B. De Farias
    • Débora S. Prusch
    • Tiago E. Heinen
    • Rafael P. Dos Santos
    • Ana L. Abujamra
    • Gilberto Schwartsmann
    • Rafael Roesler
  • View Affiliations / Copyright

    Affiliations: Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil, Laboratory of Neuropharmacology and Neural Tumor Biology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil, National Institute for Translational Medicine (INCT-TM), Porto Alegre, RS, Brazil, Children's Cancer Institute, Porto Alegre, RS, Brazil, Department of Internal Medicine, School of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
  • Pages: 148-152
    |
    Published online on: August 7, 2012
       https://doi.org/10.3892/mco.2012.7
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



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.
View Figures

Figure 1

Figure 2

Figure 3

View References

1. 

Cornelio DB, Roesler R and Schwartsmann G: Gastrin-releasing peptide receptor as a molecular target in experimental anticancer therapy. Ann Oncol. 18:1457–1466. 2007.

2. 

Patel O, Shulkes A and Baldwin GS: Gastrin-releasing peptide and cancer. Biochim Biophys Acta. 1766:23–41. 2006.

3. 

Cornelio DB, Meurer L, Roesler R and Schwartsmann G: Gastrin-releasing peptide receptor expression in cervical cancer. Oncology. 73:340–345. 2007.

4. 

Cornelio DB, Meurer L, Schwartsmann G and Roesler R: The gastrin-releasing peptide receptor as a marker of dysplastic alterations in cervical epithelial cells. Oncology. 82:90–97. 2012.

5. 

Giacchetti S, Gauvillé C, de Crémoux P, et al: Characterization, in some human breast cancer cell lines, of gastrin-releasing peptide-like receptors which are absent in normal breast epithelial cells. Int J Cancer. 46:293–298. 1990.

6. 

Gugger M and Reubi JC: Gastrin-releasing peptide receptors in non-neoplastic and neoplastic human breast. Am J Pathol. 155:2067–2076. 1999.

7. 

Halmos G, Wittliff JL and Schally AV: Characterization of bombesin/gastrin-releasing peptide receptors in human breast cancer and their relationship to steroid receptor expression. Cancer Res. 55:280–287. 1995.

8. 

Sun B, Schally AV and Halmos G: The presence of receptors for bombesin/GRP and mRNA for three receptor subtypes in human ovarian epithelial cancers. Regul Pept. 90:77–84. 2000.

9. 

Chatzistamou I, Schally AV, Szepeshazi K, et al: Inhibition of growth of ES-2 human ovarian cancers by bombesin antagonist RC-3095, and luteinizing hormone-releasing hormone antagonist Cetrorelix. Cancer Lett. 171:37–45. 2001.

10. 

Miyazaki M, Lamharzi N, Schally AV, et al: Inhibition of growth of MDA-MB-231 human breast cancer xenografts in nude mice by bombesin/gastrin-releasing peptide (GRP) antagonists RC-3940-II and RC-3095. Eur J Cancer. 34:710–717. 1998.

11. 

Yano T, Pinski J, Szepeshazi K, et al: Inhibitory effect of bombesin/gastrin-releasing peptide antagonist RC-3095 and luteinizing hormone-releasing hormone antagonist SB-75 on the growth of MCF-7 MIII human breast cancer xenografts in athymic nude mice. Cancer. 73:1229–1238. 1994.

12. 

Huang EJ and Reichardt LF: Trk receptors: roles in neuronal signal transduction. Annu Rev Biochem. 72:609–642. 2003.

13. 

Desmet CJ and Peeper DS: The neurotrophic receptor TrkB: a drug target in anti-cancer therapy? Cell Mol Life Sci. 63:755–759. 2006.

14. 

Roesler R, de Farias CB, Abujamra AL, Brunetto AL and Schwartsmann G: BDNF/TrkB signaling as an anti-tumor target. Expert Rev Anticancer Ther. 11:1473–1475. 2011.

15. 

Thiele CJ, Li Z and McKee AE: On Trk - the TrkB signal transduction pathway is an increasingly important target in cancer biology. Clin Cancer Res. 15:5962–5967. 2009.

16. 

Akil H, Perraud A, Mélin C, Jauberteau MO and Mathonnet M: Fine-tuning roles of endogenous brain-derived neurotrophic factor, TrkB and sortilin in colorectal cancer cell survival. PLoS One. 6:e250972011.

17. 

de Farias CB, Rosemberg DB, Heinen TE, et al: BDNF/TrkB content and interaction with gastrin-releasing peptide receptor blockade in colorectal cancer. Oncology. 79:430–439. 2010.

18. 

Li Z, Oh DY, Nakamura K and Thiele CJ: Perifosine-induced inhibition of Akt attenuates brain-derived neurotrophic factor/TrkB-induced chemoresistance in neuroblastoma in vivo. Cancer. 117:5412–5422. 2011.

19. 

Perez-Pinera P, Hernandez T, García-Suárez O, et al: The Trk tyrosine kinase inhibitor K252α regulates growth of lung adenocarcinomas. Mol Cell Biochem. 295:19–26. 2007.

20. 

Au CW, Siu MK, Liao X, et al: Tyrosine kinase B receptor and BDNF expression in ovarian cancers - effect on cell migration, angiogenesis and clinical outcome. Cancer Lett. 281:151–161. 2009.

21. 

Moon A, Won KY, Lee JY, et al: Expression of BDNF, TrkB, and p53 in early-stage squamous cell carcinoma of the uterine cervix. Pathology. 43:453–458. 2011.

22. 

Qiu L, Zhou C, Sun Y, et al: Crosstalk between EGFR and TrkB enhances ovarian cancer cell migration and proliferation. Int J Oncol. 29:1003–1011. 2006.

23. 

Yu X, Liu L, Cai B, He Y and Wan X: Suppression of anoikis by the neurotrophic receptor TrkB in human ovarian cancer. Cancer Sci. 99:543–552. 2008.

24. 

Patani N, Jiang WG and Mokbel K: Brain-derived neurotrophic factor expression predicts adverse pathological and clinical outcomes in human breast cancer. Cancer Cell Int. 11:232011.

25. 

Vanhecke E, Adriaenssens E, Verbeke S, et al: Brain-derived neurotrophic factor and neurotrophin-4/5 are expressed in breast cancer and can be targeted to inhibit tumor cell survival. Clin Cancer Res. 17:1741–1752. 2011.

26. 

de Farias CB, Lima RC, Lima LO, et al: Stimulation of proliferation of U138-MG glioblastoma cells by gastrin-releasing peptide in combination with agents that enhance cAMP signaling. Oncology. 75:27–31. 2008.

27. 

Flores DG, de Farias CB, Leites J, et al: Gastrin-releasing peptide receptors regulate proliferation of C6 Glioma cells through a phosphatidylinositol 3-kinase-dependent mechanism. Curr Neurovasc Res. 5:99–105. 2008.

28. 

Yano T, Pinski J, Groot K and Schally AV: Stimulation by bombesin and inhibition by bombesin/gastrin-releasing peptide antagonist RC-3095 of growth of human breast cancer cell lines. Cancer Res. 52:4545–4547. 1992.

29. 

Patel KV and Schrey MP: Activation of inositol phospholipid signaling and Ca2+ efflux in human breast cancer cells by bombesin. Cancer Res. 50:235–239. 1990.

30. 

Abujamra AL, Almeida VR, Brunetto AL, Schwartsmann G and Roesler R: A gastrin-releasing peptide receptor antagonist stimulates Neuro2α neuroblastoma cell growth: prevention by a histone deacetylase inhibitor. Cell Biol Int. 33:899–903. 2009.

31. 

Pinski J, Schally AV, Halmos G, et al: Somatostatin analogues and bombesin/gastrin-releasing peptide antagonist RC-3095 inhibit the growth of human glioblastomas in vitro and in vivo. Cancer Res. 54:5895–5901. 1994.

32. 

Czepielewski RS, Porto BN, Rizzo LB, et al: Gastrin-releasing peptide receptor (GRPR) mediates chemotaxis in neutrophils. Proc Natl Acad Sci USA. 109:547–552. 2012.

33. 

Roesler R, Luft T, Oliveira SH, et al: Molecular mechanisms mediating gastrin-releasing peptide receptor modulation of memory consolidation in the hippocampus. Neuropharmacology. 51:350–357. 2006.

34. 

Roesler R, Meller CA, Kopschina MI, et al: Intrahippocampal infusion of the bombesin/gastrin-releasing peptide antagonist RC-3095 impairs inhibitory avoidance retention. Peptides. 24:1069–1074. 2003.

35. 

Jensen RT, Battey JF, Spindel ER and Benya RV: International Union of Pharmacology. LXVIII. Mammalian bombesin receptors: nomenclature, distribution, pharmacology, signaling, and functions in normal and disease states. Pharmacol Rev. 60:1–42. 2008.

36. 

Chao C, Ives K, Hellmich HL, Townsend CM Jr and Hellmich MR: Gastrin-releasing peptide receptor in breast cancer mediates cellular migration and interleukin-8 expression. J Surg Res. 156:26–31. 2009.

37. 

Bajo AM, Schally AV, Krupa M, et al: Bombesin antagonists inhibit growth of MDA-MB-435 estrogen-independent breast cancers and decrease the expression of the ErbB-2/HER-2 oncoprotein and c-jun and c-fos oncogenes. Proc Natl Acad Sci USA. 99:3836–3841. 2002.

38. 

Chatzistamou I, Schally AV, Sun B, Armatis P and Szepeshazi K: Inhibition of growth of OV-1063 human epithelial ovarian cancers and c-jun and c-fos oncogene expression by bombesin antagonists. Br J Cancer. 83:906–913. 2000.

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Cornelio DB, De Farias CB, Prusch DS, Heinen TE, Dos Santos RP, Abujamra AL, Schwartsmann G and Roesler R: Influence of GRPR and BDNF/TrkB signaling on the viability of breast and gynecologic cancer cells. Mol Clin Oncol 1: 148-152, 2013.
APA
Cornelio, D.B., De Farias, C.B., Prusch, D.S., Heinen, T.E., Dos Santos, R.P., Abujamra, A.L. ... Roesler, R. (2013). Influence of GRPR and BDNF/TrkB signaling on the viability of breast and gynecologic cancer cells. Molecular and Clinical Oncology, 1, 148-152. https://doi.org/10.3892/mco.2012.7
MLA
Cornelio, D. B., De Farias, C. B., Prusch, D. S., Heinen, T. E., Dos Santos, R. P., Abujamra, A. L., Schwartsmann, G., Roesler, R."Influence of GRPR and BDNF/TrkB signaling on the viability of breast and gynecologic cancer cells". Molecular and Clinical Oncology 1.1 (2013): 148-152.
Chicago
Cornelio, D. B., De Farias, C. B., Prusch, D. S., Heinen, T. E., Dos Santos, R. P., Abujamra, A. L., Schwartsmann, G., Roesler, R."Influence of GRPR and BDNF/TrkB signaling on the viability of breast and gynecologic cancer cells". Molecular and Clinical Oncology 1, no. 1 (2013): 148-152. https://doi.org/10.3892/mco.2012.7
Copy and paste a formatted citation
x
Spandidos Publications style
Cornelio DB, De Farias CB, Prusch DS, Heinen TE, Dos Santos RP, Abujamra AL, Schwartsmann G and Roesler R: Influence of GRPR and BDNF/TrkB signaling on the viability of breast and gynecologic cancer cells. Mol Clin Oncol 1: 148-152, 2013.
APA
Cornelio, D.B., De Farias, C.B., Prusch, D.S., Heinen, T.E., Dos Santos, R.P., Abujamra, A.L. ... Roesler, R. (2013). Influence of GRPR and BDNF/TrkB signaling on the viability of breast and gynecologic cancer cells. Molecular and Clinical Oncology, 1, 148-152. https://doi.org/10.3892/mco.2012.7
MLA
Cornelio, D. B., De Farias, C. B., Prusch, D. S., Heinen, T. E., Dos Santos, R. P., Abujamra, A. L., Schwartsmann, G., Roesler, R."Influence of GRPR and BDNF/TrkB signaling on the viability of breast and gynecologic cancer cells". Molecular and Clinical Oncology 1.1 (2013): 148-152.
Chicago
Cornelio, D. B., De Farias, C. B., Prusch, D. S., Heinen, T. E., Dos Santos, R. P., Abujamra, A. L., Schwartsmann, G., Roesler, R."Influence of GRPR and BDNF/TrkB signaling on the viability of breast and gynecologic cancer cells". Molecular and Clinical Oncology 1, no. 1 (2013): 148-152. https://doi.org/10.3892/mco.2012.7
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team