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The role of kinin receptors in cancer and therapeutic opportunities
Open accessAbstract
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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“Captopril usage has improved the accumulation of paclitaxel-loaded nanoparticles in U87 glioma xenograft tumors [40,41,42].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [40]
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Self-citation
Metadata
- Authors
- da Costa, P. L. N., Sirois, P., Tannock, I. F., & Chammas, R.
- Affiliations
- University of Toronto (CA)
- Universidade de São Paulo (BR)
- Venue
- Cancer Letters
- Publisher
- Elsevier BV
- Published
- 2014-04
- Volume
- 345
- Issue
- 1
- Pages
- 27-38
- ISSN
- 0304-3835 (ISSN-L)
- 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
- 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 › Hematology › 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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