The role of kinin receptors in cancer and therapeutic opportunities

da Costa, Patrícia L.N.; Sirois, Pierre; Tannock, Ian F.; Chammas, Roger

doi:10.1016/j.canlet.2013.12.009

Cited by 134Coagulation, Bradykinin, Polyphosphates, and AngioedemaRenin-Angiotensin System StudiesPineapple and bromelain studies

The role of kinin receptors in cancer and therapeutic opportunities

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da Costa, Patrícia L.N., Sirois, Pierre, Tannock, Ian F., Chammas, Roger·2014·Cancer Letters

DOI 10.1016/j.canlet.2013.12.009

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Abstract

Kinins are generated within inflammatory tissue microenvironments, where they exert diverse functions, including cell proliferation, leukocyte activation, cell migration, endothelial cell activation and nociception. These pleiotropic functions depend on signaling through two cross talking receptors, the constitutively expressed kinin receptor 2 (B2R) and the inducible kinin receptor 1 (B1R). We have reviewed evidence, which supports the concept that kinin receptors, especially kinin receptor 1, are promising targets for cancer therapy, since (1) many tumor cells express aberrantly high levels of these receptors; (2) some cancers produce kinins and use them as autocrine factors to stimulate their growth; (3) activation of kinin receptors leads to activation of macrophages, dendritic cells and other cells from the tumor microenvironment; (4) kinins have pro-angiogenic properties; (5) kinin receptors have been implicated in cancer migration, invasion and metastasis; and (6) selective antagonists for either B1R or B2R have shown anti-proliferative, anti-inflammatory, anti-angiogenic and anti-migratory properties. The multiple cross talks between kinin receptors and renin-angiotensin system (RAS) as well as its implications for targeting KKS or RAS for the treatment of malignancies are also discussed. It is expected that B1R antagonists would interfere less with housekeeping functions and therefore would be attractive compounds to treat selected types of cancer. Reliable clinical studies are needed to establish the translatability of these data to human settings and the usefulness of kinin receptor antagonists.

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From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [40]

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Strategies to improve the EPR effect: A mechanistic perspective and clinical translation
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Kinin and Purine Signaling Contributes to Neuroblastoma Metastasis
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Targeting Cancer using Curcumin Encapsulated Vesicular Drug Delivery Systems
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The complement and contact activation systems: partnership in pathogenesis beyond angioedema
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A modular map of Bradykinin-mediated inflammatory signaling network
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Function and structure of bradykinin receptor 2 for drug discovery
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Bradykinin stimulates IL-6 production and cell invasion in colorectal cancer cells
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TiO2 nanoparticles tested in a novel screening whole human blood model of toxicity trigger adverse activation of the kallikrein system at low concentrations
Ekstrand‐Hammarström, B., Hong, J., Davoodpour, P., Sandholm, K., Ekdahl, K. N., Bucht, A., & Nilsson, B. (2015) · Biomaterials · doi:10.1016/j.biomaterials.2015.01.031 · Cited by 51 · see citing works
The Bradykinin-BDKRB1 Axis Regulates Aquaporin 4 Gene Expression and Consequential Migration and Invasion of Malignant Glioblastoma Cells via a Ca2+-MEK1-ERK1/2-NF-κB Mechanism
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A Systematic Review of Molecular Imaging Agents Targeting Bradykinin B1 and B2 Receptors
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Kinin-B1 Receptor Stimulation Promotes Invasion and is Involved in Cell-Cell Interaction of Co-Cultured Glioblastoma and Mesenchymal Stem Cells
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Bradykinin B1 receptor contributes to interleukin-8 production and glioblastoma migration through interaction of STAT3 and SP-1
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18 F-Trifluoroborate Derivatives of [Des-Arg 10 ]Kallidin for Imaging Bradykinin B1 Receptor Expression with Positron Emission Tomography
Liu, Z., Amouroux, G., Zhang, Z., Pan, J., Hundal-Jabal, N., Colpo, N., Lau, J., Perrin, D. M., Bénard, F., & Lin, K. (2015) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.5b00003 · Cited by 42 · see citing works
Bradykinin promotes migration and invasion of hepatocellular carcinoma cells through TRPM7 and MMP2
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Mechanisms involved in kinin-induced glioma cells proliferation: the role of ERK1/2 and PI3K/Akt pathways
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Advancement of cell-penetrating peptides in combating triple-negative breast cancer
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The contact system in liver injury
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Cryo-EM structures of human bradykinin receptor-Gq proteins complexes
Shen, J., Zhang, D., Fu, Y., Chen, A., Yang, X., & Zhang, H. (2022) · Nature Communications · doi:10.1038/s41467-022-28399-1 · Cited by 37 · see citing works
Novel water-soluble lignin derivative BP-Cx-1: identification of components and screening of potential targets in silico and in vitro
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Influence of calcium ion-modified implant surfaces in protein adsorption and implant integration
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Bradykinin Promotes Cell Proliferation, Migration, Invasion, and Tumor Growth of Gastric Cancer Through ERK Signaling Pathway
Wang, G., Sun, J., Liu, G., Fu, Y., & Zhang, X. (2017) · Journal of Cellular Biochemistry · doi:10.1002/jcb.26100 · Cited by 33 · see citing works
Primary Role for Kinin B1 and B2 Receptors in Glioma Proliferation
Nicoletti, N. F., Sénécal, J., da Silva, V. D., Roxo, M. R. R., Ferreira, N. P., Morais, R. L., Pesquero, J. B., Campos, M. M., Couture, R., & Morrone, F. B. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-0265-9 · Cited by 30 · see citing works
Neuropeptide-induced modulation of carcinogenesis in a metastatic breast cancer cell line (MDA-MB-231LUC+)
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A human whole-blood model to study the activation of innate immunity system triggered by nanoparticles as a demonstrator for toxicity
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Serum bradykinin levels as a diagnostic marker in cervical cancer with a potential mechanism to promote VEGF expression via BDKRB2
Zhou, Y., Wang, W., Wei, R., Jiang, G., Li, F., Chen, X., Wang, X., Long, S., Ma, D., & Xi, L. (2019) · International Journal of Oncology · doi:10.3892/ijo.2019.4792 · Cited by 29 · see citing works
Overexpressed Receptors and Proteins in Lung Cancer
Gorain, B., Bhattamisra, S. K., Choudhury, H., Nandi, U., Pandey, M., & Kesharwani, P. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-815720-6.00003-4 · Cited by 28 · see citing works
ATP/pH Dual Responsive Nanoparticle with d ‐[des‐Arg10]Kallidin Mediated Efficient In Vivo Targeting Drug Delivery
Zhang, Y., Lü, Y., Wang, F., An, S., Zhang, Y., Sun, T., Zhu, J., & Jiang, C. (2016) · Small · doi:10.1002/smll.201602494 · Cited by 28 · see citing works
Glioblastoma‐mesenchymal stem cell communication modulates expression patterns of kinin receptors: Possible involvement of bradykinin in information flow
Pillat, M. M., Oliveira, M. N., Motaln, H., Breznik, B., Glaser, T., Lah, T. T., & Ulrich, H. (2015) · Cytometry Part A · doi:10.1002/cyto.a.22800 · Cited by 27 · see citing works
The role of complement in the tumor microenvironment
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Unravelling the role of tumor microenvironment responsive nanobiomaterials in spatiotemporal controlled drug delivery for lung cancer therapy
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Imaging Bradykinin B1 Receptor with68Ga-Labeled [des-Arg10]Kallidin Derivatives: Effect of the Linker on Biodistribution and Tumor Uptake
Amouroux, G., Pan, J., Jenni, S., Zhang, C., Zhang, Z., Hundal-Jabal, N., Colpo, N., Liu, Z., Bénard, F., & Lin, K. (2015) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.5b00070 · Cited by 24 · see citing works
Targeting intracellular B2 receptors using novel cell-penetrating antagonists to arrest growth and induce apoptosis in human triple-negative breast cancer
Dubuc, C., Savard, M., Bovenzi, V., Lessard, A., Fortier, A., Côté, J., Neugebauer, W. A., Rizzolio, F., Geha, S., Giordano, A., et al. (2018) · Oncotarget · doi:10.18632/oncotarget.24009 · Cited by 24 · see citing works
Onco-GPCR signaling and dysregulated expression of microRNAs in human cancer
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Antitumor activity of cell‐penetrant kinin B1 receptor antagonists in human triple‐negative breast cancer cells
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Kinin receptors in skin wound healing
Soley, B. D. S., Morais, R. L., Pesquero, J. B., Bäder, M., Otuki, M. F., & Cabrini, D. A. (2016) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2016.01.007 · Cited by 23 · see citing works
Enhanced nanodrug delivery in tumors after near‐infrared photoimmunotherapy
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BDKRB2 is a novel EMT-related biomarker and predicts poor survival in glioma
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Self-citation

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Authors: da Costa, P. L. N., Sirois, P., Tannock, I. F., & Chammas, R.
Affiliations: University of Toronto (CA)
Universidade de São Paulo (BR)
ORCID: Tannock, Ian F.
Chammas, Roger
Venue: Cancer Letters
Publisher: Elsevier BV
Published: 2014-04
Volume: 345
Issue: 1
Pages: 27-38
ISSN: 0304-3835 (ISSN-L)
DOI: 10.1016/j.canlet.2013.12.009
OpenAlex: W2090131666
Cited by: 133
References: 205
Citations by year: 2026: 3 · 2025: 8 · 2024: 10 · 2023: 11 · 2022: 16 · 2021: 17 · 2020: 8 · 2019: 6 · 2018: 17 · 2017: 6 · 2016: 21 · 2015: 6 · 2014: 4
FWCI: 1.41
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by-nc-nd/3.0/ (vor)
Locations: Cancer Letters (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Funders: Fundação de Amparo à Pesquisa do Estado de São Paulo
Topics: Health Sciences › Medicine › Genetics › Coagulation, Bradykinin, Polyphosphates, and Angioedema
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pineapple and bromelain studies
Keywords: kinin receptors, B1 receptor, bradykinin B2 receptor, kinin receptor antagonists, cancer therapy, tumor microenvironment, angiogenesis, metastasis, renin-angiotensin system, autocrine signaling, macrophage activation, dendritic cells
MeSH terms: Animals, Humans, Neoplasms, Signal Transduction, Receptor, Bradykinin B2, Receptor, Bradykinin B1, Molecular Targeted Therapy, Bradykinin B2 Receptor Antagonists, Bradykinin B1 Receptor Antagonists

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The role of kinin receptors in cancer and therapeutic opportunities

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