Evidence map›Paper›PMID 32155954›Full record

ArticleCells2020

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

Dimas Carolina Belisario, Muhlis Akman, Martina Godel, Virginia Campani, Maria Pia Patrizio, Lorena Scotti, Claudia Maria Hattinger, Giuseppe De De Rosa, Massimo Donadelli, Massimo Serra and 2 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Cells, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
2.6field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 47 citations in OpenAlex.

  1. Article
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  11. TFEB controls sensitivity to chemotherapy and immuno-killing in non-small cell lung cancer.Journal of experimental & clinical cancer research : CR · 2024
    Article
  12. Article
  13. Review
  14. Emerging roles of long non-coding RNAs in osteosarcoma.Frontiers in molecular biosciences · 2024
    Review
  15. Article
  16. Article
  17. Article
  18. Strategies to Overcome Resistance to Immune-Based Therapies in Osteosarcoma.International journal of molecular sciences · 2023
    Review
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 1 country.

Dimas Carolina BelisarioDepartment of Oncology, University of Torino, via Santena 5/bis, 10126 Torino, Italy.
Muhlis AkmanDepartment of Oncology, University of Torino, via Santena 5/bis, 10126 Torino, Italy.
Martina GodelDepartment of Oncology, University of Torino, via Santena 5/bis, 10126 Torino, Italy.
Virginia CampaniDepartment of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy.
Maria Pia PatrizioIRCCS Istituto Ortopedico Rizzoli, Laboratory of Experimental Oncology, Pharmacogenomics and Pharmacogenetics Research Unit, via di Barbiano, 1/10, 40136 Bologna, Italy.
Lorena ScottiDepartment of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy.
Claudia Maria HattingerIRCCS Istituto Ortopedico Rizzoli, Laboratory of Experimental Oncology, Pharmacogenomics and Pharmacogenetics Research Unit, via di Barbiano, 1/10, 40136 Bologna, Italy.
Giuseppe De De RosaDepartment of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy.ORCID 0000-0002-1210-1269
Massimo DonadelliDepartment of Neurosciences, Biomedicine and Movement Sciences, Section of Biochemistry, University of Verona, Piazzale L.A. Scuro 10, 37134 Verona, Italy.ORCID 0000-0001-9224-9230
Massimo SerraIRCCS Istituto Ortopedico Rizzoli, Laboratory of Experimental Oncology, Pharmacogenomics and Pharmacogenetics Research Unit, via di Barbiano, 1/10, 40136 Bologna, Italy.ORCID 0000-0003-0742-1177
Joanna KopeckaDepartment of Oncology, University of Torino, via Santena 5/bis, 10126 Torino, Italy.
Chiara RigantiDepartment of Oncology, University of Torino, via Santena 5/bis, 10126 Torino, Italy.ORCID 0000-0001-9787-4836
University of Turin · ITIstituto Ortopedico Rizzoli · ITUniversity of Naples Federico II · ITUniversity of Verona · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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 axis up-regulates ABCB1. Targeting the farnesylation of Ras with self-assembling nanoparticles encapsulating zoledronic acid (NZ) simultaneously inhibited both axes. In humanized mice, NZ reduced the growth of chemo-immune-resistant osteosarcomas, increased intratumor necro-apoptosis, and ABCA1/ABCB1 ratio and Vγ9Vδ2 T-cell infiltration. We suggest that the ABCB1

Indexed as

AnimalsATP Binding Cassette Transporter 1ATP Binding Cassette Transporter, Subfamily BBone NeoplasmsCell Line, TumorDoxorubicinDrug Resistance, NeoplasmFemaleHeterograftsHumansMiceMice, Inbred NODMice, SCIDOsteosarcomaT-LymphocytesTransfectionABCA1 protein, humanABCB1 protein, humanATP Binding Cassette Transporter 1ATP Binding Cassette Transporter, Subfamily BDoxorubicinABCA1ABCB1doxorubicin resistanceosteosarcomaVγ9Vδ2 T-cells

Identifiers

PMID32155954
PMCPMC7140509
OpenAlexW3009480075

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.