ArticleCancer biology & therapy2013
Endothelin receptor-A is required for the recruitment of antitumor T cells and modulates chemotherapy induction of cancer stem cells.
Article in Cancer biology & therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 49 citations in OpenAlex.
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- Two-Sample Network Mendelian Randomization and Single-Cell Analysis Reveal the Causal Associations and Underlying Mechanisms Between Antihypertensive Drugs and Kidney Cancer.Journal of Cancer · 2025Article
- The Role of Cancer Stem Cell Markers in Ovarian Cancer.Cancers · 2023Review
- Targeting the Endothelin-1 pathway to reduce invasion and chemoresistance in gallbladder cancer cells.Cancer cell international · 2023Article
- Deciphering Common Traits of Breast and Ovarian Cancer Stem Cells and Possible Therapeutic Approaches.International journal of molecular sciences · 2023Review
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- Endothelin Receptor Antagonists: Status Quo and Future Perspectives for Targeted Therapy.Journal of clinical medicine · 2020Review
- Endothelin-converting enzyme-1c promotes stem cell traits and aggressiveness in colorectal cancer cells.Molecular oncology · 2020Article
- The Paradox of Cancer Immune Exclusion: Immune Oncology Next Frontier.Cancer treatment and research · 2020Article
- Next Generation Imaging Techniques to Define Immune Topographies in Solid Tumors.Frontiers in immunology · 2020Review
- Surface markers of cancer stem-like cells of ovarian cancer and their clinical relevance.Contemporary oncology (Poznan, Poland) · 2018Review
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- Blocking endothelin-1-receptor/β-catenin circuit sensitizes to chemotherapy in colorectal cancer.Cell death and differentiation · 2017Article
- STROBE-compliant integrin through focal adhesion involve in cancer stem cell and multidrug resistance of ovarian cancer.Medicine · 2017Observational
- β-arrestin1 at the cross-road of endothelin-1 signaling in cancer.Journal of experimental & clinical cancer research : CR · 2016Review
- Endothelin A receptor drives invadopodia function and cell motility through the β-arrestin/PDZ-RhoGEF pathway in ovarian carcinoma.Oncogene · 2016Article
- Nuclear β-arrestin1 is a critical cofactor of hypoxia-inducible factor-1α signaling in endothelin-1-induced ovarian tumor progression.Oncotarget · 2016Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe endothelin receptor-A (ETRA) plays an important role in tumor cell migration, metastasis, and proliferation. The endothelin receptor B (ETRB) plays a critical role in angiogenesis and the inhibition of anti-tumor immune cell recruitment. Thus dual blockade of ETRA and ETRB could have significant anti-tumor effects.
resultsDual ETRA/ETRB blockade with macitentan (or the combination of the ETRA and ETRB antagonists BQ123 and BQ788) did not enhance antitumor immune cell recruitment. In vitro studies demonstrate that ETRA inhibition prevents the induction of ICAM1 necessary for immune cell recruitment. When used as a single agent against human tumor xenografts, macitentan demonstrated non-significant anti-tumor activity. However, when used in combination with chemotherapy, macitentan specifically reduced tumor growth in cell lines with CD133+ cancer stem cells. We found that ETRA is primarily expressed on CD133+ CSC in both cell lines and primary human tumor cells. ETRA inhibition of CSC prevented chemotherapy induced increases in tumor stem cells. Furthermore, ETRA inhibition in combination with chemotherapy reduced the formation of tumor spheres.
methodsWe tested the dual ETRA/ETRB antagonist macitentan in conjunction with (1) an anti-tumor vaccine and (2) chemotherapy, in order to assess the impact of dual ETRA/ETRB blockade on anti-tumor immune cell infiltration and ovarian tumor growth. In vitro murine and human cell line, tumor sphere assays and tumor xenograft models were utilized to evaluate the effect of ETRA/ETRB blockade on cell proliferation, immune cell infiltration and cancer stem cell populations.
conclusionsThese studies indicate a critical role for ETRA in the regulation of immune cell recruitment and in the CSC resistance to chemotherapy.
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