ABCA1/ABCB1 Ratio Determines Chemo- and Immune-Sensitivity in Human Osteosarcoma.

Cells
Dimas Carolina BelisarioChiara Riganti

Abstract

The ATP Binding Cassette transporter B1 (ABCB1) induces chemoresistance in osteosarcoma, because it effluxes doxorubicin, reducing the intracellular accumulation, toxicity, and immunogenic cell death induced by the drug. The ATP Binding Cassette transporter A1 (ABCA1) effluxes isopentenyl pyrophosphate (IPP), a strong activator of anti-tumor Vγ9Vδ2 T-cells. Recruiting this population may represent an alternative strategy to rescue doxorubicin efficacy in ABCB1-expressing osteosarcoma. In this work, we analyzed how ABCA1 and ABCB1 are regulated in osteosarcoma, and if increasing the ABCA1-dependent activation of Vγ9Vδ2 T-cells could be an effective strategy against ABCB1-expressing osteosarcoma. We used 2D-cultured doxorubicin-sensitive human U-2OS and Saos-2 cells, their doxorubicin-resistant sublines (U-2OS/DX580 and Saos-2/DX580), and 3D cultures of U-2OS and Saos-2 cells. DX580-sublines and 3D cultures had higher levels of ABCB1 and higher resistance to doxorubicin than parental cells. Surprisingly, they had reduced ABCA1 levels, IPP efflux, and Vγ9Vδ2 T-cell-induced killing. In these chemo-immune-resistant cells, the Ras/Akt/mTOR axis inhibits the ABCA1-transcription induced by Liver X Receptor α (LXRα); Ras/ERK1/2/HIF-1α a...Continue Reading

References

Nov 23, 1995·The New England Journal of Medicine·N BaldiniM Campanacci
Jul 9, 1993·International Journal of Cancer. Journal International Du Cancer·C AubertP Metge
Feb 1, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Massimo SerraPiero Picci
Oct 26, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Anke J RoelofsMichael J Rogers
Apr 14, 2010·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Sergio Granados-PrincipalM Carmen Ramirez-Tortosa
Oct 16, 2010·Journal of Controlled Release : Official Journal of the Controlled Release Society·Joanna KopeckaChiara Riganti
Nov 9, 2010·International Journal of Pharmaceutics·G SalzanoG De Rosa
Apr 19, 2011·International Journal of Immunopathology and Pharmacology·E CiminiC Agrati
Jul 15, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Barbara CastellaMassimo Massaia
Jun 20, 2013·Cholesterol·Anouar Hafiane, Jacques Genest
Dec 30, 2014·Oncotarget·Iris Chiara SalaroglioChiara Riganti
Mar 7, 2015·Immunology and Cell Biology·Joanna HalkiasHeather J Melichar
May 13, 2015·Frontiers in Immunology·Lucillia BezuGuido Kroemer
May 30, 2015·Expert Opinion on Emerging Drugs·Claudia Maria HattingerMassimo Serra
Jul 21, 2015·Nature Medicine·Andrew J GentlesAsh A Alizadeh
Oct 10, 2015·Nature Reviews. Immunology·Bruno Silva-SantosHåkan Norell
Jun 22, 2016·The Lancet Oncology·Sophie Piperno-NeumannUNKNOWN French Sarcoma Group (GSF-GETO)
Nov 1, 2016·Nature Reviews. Immunology·Lorenzo GalluzziGuido Kroemer
Dec 2, 2017·Journal of Controlled Release : Official Journal of the Controlled Release Society·Elena GazzanoChiara Riganti
Dec 24, 2017·Cancer Research·Ruth NussinovHyunbum Jang
Jan 11, 2018·Journal of Translational Medicine·Yijing ZhaoJiuwei Cui
Aug 30, 2018·Journal of Experimental & Clinical Cancer Research : CR·Xin XiaoZheng Guo
Nov 6, 2018·Frontiers in Immunology·Carolina Maiumi Shiromizu, Carolina Cristina Jancic
Nov 30, 2018·Journal of Experimental & Clinical Cancer Research : CR·Iris C SalaroglioJoanna Kopecka
Feb 19, 2019·Critical Reviews in Biochemistry and Molecular Biology·Daniel D WallerYoula S Tsantrizos
Aug 14, 2019·Expert Opinion on Emerging Drugs·Claudia Maria HattingerMassimo Serra

❮ Previous
Next ❯

Citations

Nov 10, 2020·The International Journal of Biochemistry & Cell Biology·Joanna KopeckaChiara Riganti
Jan 6, 2021·Cancers·Zachary D Prudowsky, Jason T Yustein
Jun 22, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Zenghui GuZhaoming Ye
Jul 27, 2021·Journal of Bone Oncology·Javier Munoz-GarciaDominique Heymann
Apr 14, 2021·Current Drug Targets·Maria Manuela EstevinhoJoão Carvalho

❮ Previous
Next ❯

Methods Mentioned

BETA
Assay
pull-down
Immunoprecipitation
PCR
nuclear translocation
xenografts

Clinical Trials Mentioned

NCT00470223

Software Mentioned

R2
Matinspector
InCyte
SPSS Statistics
Statistical Package for Social Science ( SPSS )

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Related Papers

Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society
Zhaoxu LiZ Ye
Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research
E CiminiChiara Agrati
The Journal of Immunology : Official Journal of the American Association of Immunologists
Renée C G de BruinHans J van der Vliet
© 2021 Meta ULC. All rights reserved