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Adenosine 2B Receptor Expression on Cancer Cells Promotes Metastasis

Deepak Mittal1, Debottam Sinha2, Deborah Barkauskas3

  • 1Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia. School of Medicine, The University of Queensland, Herston, Queensland, Australia.

Cancer Research
|May 26, 2016
PubMed

Insights

An adenosine 2B receptor inhibitor (A2BRi) effectively reduces cancer metastasis in preclinical models. This inhibition impacts tumor cell viability and shows promise when combined with existing cancer therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Adenosine signaling is implicated in cancer progression, inflammation, and treatment response.
  • The adenosine 2B receptor (A2BR) is a key mediator of adenosine's effects in cancer.

Purpose of the Study:

  • To investigate the therapeutic potential of targeting the adenosine 2B receptor (A2BR) in reducing cancer metastasis.
  • To evaluate the efficacy of an A2BR inhibitor (A2BRi) alone and in combination with chemotherapy or immune checkpoint inhibitors.

Main Methods:

  • Utilized mouse models of melanoma and triple-negative breast cancer (TNBC) metastasis.
  • Assessed the impact of A2BR inhibition on experimental and spontaneous metastasis.
  • Examined the role of A2BR expression in cancer cells and host immune cells.
  • Investigated the effects of A2BR knockdown on cancer cell viability and cell cycle progression in vitro.

Main Results:

  • A2BR inhibition significantly decreased both experimental and spontaneous metastasis in mouse models.
  • A2BRi demonstrated synergistic effects when combined with chemotherapy and immune checkpoint inhibitors.
  • Decreased metastasis was observed independently of host A2BR expression and immune cell populations.
  • Knockdown of A2BR in cancer cells reduced their metastatic potential, viability, and colony formation.
  • Human TNBC cell lines exhibited higher A2BR expression compared to other breast cancer subtypes, correlating with poorer prognosis.

Conclusions:

  • Tumor-intrinsic A2BR plays a significant role in promoting cancer metastasis.
  • Targeting A2BR with inhibitors represents a promising therapeutic strategy for reducing metastasis in cancers like TNBC.
  • A2BR is a viable therapeutic target for intervention in cancer metastasis.

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