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Cited by 32Cancer, Lipids, and MetabolismCholesterol and Lipid MetabolismDrug Transport and Resistance Mechanisms

Myeloid-specific genetic ablation of ATP-binding cassette transporter ABCA1 is protective against cancer

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Zamanian-Daryoush, Maryam, Lindner, Daniel J., DiDonato, Joseph A., Wagner, Matthew, Buffa, Jennifer, Rayman, Patricia, Parks, John S., Westerterp, Marit +2 more·2017·Oncotarget
DOI 10.18632/oncotarget.18666PMC PMC5641104
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Abstract

// Maryam Zamanian-Daryoush 1 , Daniel J. Lindner 2 , Joseph A. DiDonato 1 , Matthew Wagner 1 , Jennifer Buffa 1 , Patricia Rayman 3 , John S. Parks 4 , Marit Westerterp 5 , Alan R. Tall 5 and Stanley L. Hazen 1, 6 1 Department of Cellular & Molecular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA 2 Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA 3 Department of Immunology, Cleveland Clinic, Cleveland, OH 44195, USA 4 Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA 5 Department of Medicine, Columbia University, College of Physicians and Surgeons 8-401, New York, NY 10032, USA 6 Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA Correspondence to: Stanley L. Hazen, email: hazens@ccf.org Keywords: cancer, apolipoprotein, myeloid cell, cholesterol, ABC transporter Received: March 18, 2016 Accepted: May 23, 2017 Published: June 27, 2017 ABSTRACT Increased circulating levels of apolipoprotein A-I (apoA-I), the major protein of high-density lipoprotein (HDL), by genetic manipulation or infusion, protects against melanoma growth and metastasis. Herein, we explored potential roles in melanoma tumorigenesis for host scavenger receptor class B, type 1 (SR-B1), and ATP-binding cassette transporters A1 (ABCA1) and G1 (ABCG1), all mediators of apoA-I and HDL sterol and lipid transport function. In a syngeneic murine melanoma tumor model, B16F10, mice with global deletion of SR-B1 expression exhibited increased plasma HDL cholesterol (HDLc) levels and decreased tumor volume, indicating host SR-B1 does not directly contribute to HDL-associated anti-tumor activity. In mice with myeloid-specific loss of ABCA1 ( Abca1 -M/-M ; A1 -M/-M ), tumor growth was inhibited by ~4.8-fold relative to wild type (WT) animals. Abcg1 -M/-M (G1 -M/-M ) animals were also protected by 2.5-fold relative to WT, with no further inhibition of tumor growth in Abca1 / Abcg1 myeloid-specific double knockout animals (DKO). Analyses of tumor-infiltrating immune cells revealed a correlation between tumor protection and decreased presence of the immune suppressive myeloid-derived suppressor cell (MDSC) subsets, Ly-6G + Ly-6C Lo and Ly-6G neg Ly-6C Hi cells. The growth of the syngeneic MB49 murine bladder cancer cells was also inhibited in A1 -M/-M mice. Collectively, our studies provide further evidence for an immune modulatory role for cholesterol homeostasis pathways in cancer.

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  • Knockdown of ABCG1 resulted in inhibited tumor growth, but in a different study this required a physiologic challenge (western diet, age or genetic model of hypercholesterolemia).

    “Knockdown of the related transporter ABCG1 also resulted in inhibited tumor growth (75), but in a different study this required a physiologic challenge (western diet, age or genetic model of hypercholesterolemia) (76).”

    From Cholesterol efflux protein, ABCA1, supports anticancer functions of myeloid immune cells (2026) · cites this paper as [75]

    The Discussion (page unavailable) reports that a different study found increased tumor immunity after Abcg1 deletion in young mice on a Western-type diet, but not normal chow, and protection in aged mice on chow. Our copy does not report a genetic model of hypercholesterolemia as another condition in that study; it also says the present study observed protection without the diet or age requirement. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • A previous report indicated that myeloid cell loss of ABCA1 decreased B16-F10 melanoma and MB49 bladder tumor growth.

    “However, a previous report indicated that myeloid cell loss of ABCA1 decreased B16-F10 melanoma and MB49 bladder tumor growth (75).”

    From Cholesterol efflux protein, ABCA1, supports anticancer functions of myeloid immune cells (2026) · cites this paper as [75]

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Authors
Zamanian-Daryoush, M., Lindner, D. J., DiDonato, J. A., Wagner, M., Buffa, J., Rayman, P., Parks, J. S., Westerterp, M., Tall, A. R., & Hazen, S. L.
Affiliations
  • Cleveland Clinic (US)
  • Wake Forest University Health Sciences (US)
  • Columbia University (US)
Corresponding author
Hazen, Stanley L.
ORCID
Venue
Oncotarget
Publisher
Impact Journals, LLC
Published
2017-06-27
Volume
8
Issue
42
Pages
71965-71980
ISSN
1949-2553 (ISSN-L)
DOI
10.18632/oncotarget.18666
PMC
PMC5641104
OpenAlex
W2732064590
Cited by
32
References
0
Citations by year
2026: 1 · 2025: 5 · 2023: 6 · 2022: 2 · 2021: 4 · 2020: 6 · 2019: 4 · 2018: 4
FWCI
1.29
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Oncotarget (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (acceptedVersion, cc-by)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
Funders
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (R01HL119962, R01HL128300, P01HL076491)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
ABCA1, ABCG1, scavenger receptor class B type I, apolipoprotein A-I, high-density lipoprotein, melanoma, tumor growth, myeloid cells, HDL cholesterol, sterol transport, anticancer activity, gene ablation, B16F10 melanoma, metastasis, host defense against cancer, lipoprotein metabolism

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