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

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, t...

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Autores principales: Zamanian-Daryoush, Maryam, Lindner, Daniel J., DiDonato, Joseph A., Wagner, Matthew, Buffa, Jennifer, Rayman, Patricia, Parks, John S., Westerterp, Marit, Tall, Alan R., Hazen, Stanley L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641104/
https://www.ncbi.nlm.nih.gov/pubmed/29069761
http://dx.doi.org/10.18632/oncotarget.18666
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author Zamanian-Daryoush, Maryam
Lindner, Daniel J.
DiDonato, Joseph A.
Wagner, Matthew
Buffa, Jennifer
Rayman, Patricia
Parks, John S.
Westerterp, Marit
Tall, Alan R.
Hazen, Stanley L.
author_facet Zamanian-Daryoush, Maryam
Lindner, Daniel J.
DiDonato, Joseph A.
Wagner, Matthew
Buffa, Jennifer
Rayman, Patricia
Parks, John S.
Westerterp, Marit
Tall, Alan R.
Hazen, Stanley L.
author_sort Zamanian-Daryoush, Maryam
collection PubMed
description 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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spelling pubmed-56411042017-10-24 Myeloid-specific genetic ablation of ATP-binding cassette transporter ABCA1 is protective against cancer Zamanian-Daryoush, Maryam Lindner, Daniel J. DiDonato, Joseph A. Wagner, Matthew Buffa, Jennifer Rayman, Patricia Parks, John S. Westerterp, Marit Tall, Alan R. Hazen, Stanley L. Oncotarget Research Paper 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. Impact Journals LLC 2017-06-27 /pmc/articles/PMC5641104/ /pubmed/29069761 http://dx.doi.org/10.18632/oncotarget.18666 Text en Copyright: © 2017 Zamanian-Daryoush et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Zamanian-Daryoush, Maryam
Lindner, Daniel J.
DiDonato, Joseph A.
Wagner, Matthew
Buffa, Jennifer
Rayman, Patricia
Parks, John S.
Westerterp, Marit
Tall, Alan R.
Hazen, Stanley L.
Myeloid-specific genetic ablation of ATP-binding cassette transporter ABCA1 is protective against cancer
title Myeloid-specific genetic ablation of ATP-binding cassette transporter ABCA1 is protective against cancer
title_full Myeloid-specific genetic ablation of ATP-binding cassette transporter ABCA1 is protective against cancer
title_fullStr Myeloid-specific genetic ablation of ATP-binding cassette transporter ABCA1 is protective against cancer
title_full_unstemmed Myeloid-specific genetic ablation of ATP-binding cassette transporter ABCA1 is protective against cancer
title_short Myeloid-specific genetic ablation of ATP-binding cassette transporter ABCA1 is protective against cancer
title_sort myeloid-specific genetic ablation of atp-binding cassette transporter abca1 is protective against cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641104/
https://www.ncbi.nlm.nih.gov/pubmed/29069761
http://dx.doi.org/10.18632/oncotarget.18666
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