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Primary research
Shay Bracha
Texas A and M University: Texas A&M University College Station
Corresponding Author
ORCiD: https://orcid.org/0000-0002-0406-2079
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Osteosarcoma patients often experience poor outcomes despite chemotherapy treatment, likely due in part to various mechanisms of tumor cell innate and/or acquired drug resistance. Exosomes, microvesicles secreted by cells, have been shown to play a role in drug resistance, but a comprehensive protein signature relating to osteosarcoma carboplatin resistance has not been fully characterized.
Methods
In this study, cell lysates and exosomes from two derivatives (HMPOS-2.5R and HMPOS-10R) of the HMPOS osteosarcoma cell line generated by repeated carboplatin treatment and recovery, were characterized proteomically by mass spectrometry. Protein cargos of circulating serum exosomes from dogs with naturally occurring osteosarcoma, were also assessed by mass spectrometry, to identify biomarkers that discriminate between good and poor responders to carboplatin therapy.
Results
Both cell lysates and exosomes exhibited distinct protein signatures related to drug resistance. Furthermore, exosomes from the resistant HMPOS-2.5R cell line were found to transfer drug resistance to drug-sensitive HMPOS cells. The comparison of serum exosomes from dogs with a favorable disease-free interval [DFI] of >300 days, and dogs with <100 days DFI revealed a proteomic signature that could discriminate between the two cohorts with high accuracy. Furthermore, when the patient’s exosomes were compared to exosomes isolated from carboplatin resistant cell lines, several putative biomarkers were found to be shared.
Conclusions
The findings of this study highlight the significance of exosomes in the potential transfer of drug resistance, and the discovery of novel biomarkers for the development of liquid biopsies to better guide personalized chemotherapy treatment.
Keywords
Osteosarcoma, exosomes, carboplatin, drug resistance, canine
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CURRENT STATUS: Under Review
Version 1
Posted 25 Feb, 2021
No community comments so far
Editorial decision: Minor revision
On 14 Mar, 2021
Review #2 received
Received 12 Mar, 2021
Review #1 received
Received 06 Mar, 2021
Reviewer #3 agreed
On 28 Feb, 2021
Reviewer #2 agreed
On 27 Feb, 2021
Reviewer #1 agreed
On 26 Feb, 2021
Reviews received
Received 26 Feb, 2021
Reviewers invited
Invitations sent on 20 Feb, 2021
Editor assigned
On 16 Feb, 2021
Submission checks complete
On 16 Feb, 2021
Editor invited
On 16 Feb, 2021
First submitted
On 13 Feb, 2021
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Subject Areas
Cancer Biology
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A new preprint design is coming!
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This preprint is under consideration at Cancer Cell International. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Primary research
Shay Bracha
Texas A and M University: Texas A&M University College Station
Corresponding Author
ORCiD: https://orcid.org/0000-0002-0406-2079
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 25 Feb, 2021
No community comments so far
Editorial decision: Minor revision
On 14 Mar, 2021
Review #2 received
Received 12 Mar, 2021
Review #1 received
Received 06 Mar, 2021
Reviewer #3 agreed
On 28 Feb, 2021
Reviewer #2 agreed
On 27 Feb, 2021
Reviewer #1 agreed
On 26 Feb, 2021
Reviews received
Received 26 Feb, 2021
Reviewers invited
Invitations sent on 20 Feb, 2021
Editor assigned
On 16 Feb, 2021
Submission checks complete
On 16 Feb, 2021
Editor invited
On 16 Feb, 2021
First submitted
On 13 Feb, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cancer Biology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Osteosarcoma patients often experience poor outcomes despite chemotherapy treatment, likely due in part to various mechanisms of tumor cell innate and/or acquired drug resistance. Exosomes, microvesicles secreted by cells, have been shown to play a role in drug resistance, but a comprehensive protein signature relating to osteosarcoma carboplatin resistance has not been fully characterized.
Methods
In this study, cell lysates and exosomes from two derivatives (HMPOS-2.5R and HMPOS-10R) of the HMPOS osteosarcoma cell line generated by repeated carboplatin treatment and recovery, were characterized proteomically by mass spectrometry. Protein cargos of circulating serum exosomes from dogs with naturally occurring osteosarcoma, were also assessed by mass spectrometry, to identify biomarkers that discriminate between good and poor responders to carboplatin therapy.
Results
Both cell lysates and exosomes exhibited distinct protein signatures related to drug resistance. Furthermore, exosomes from the resistant HMPOS-2.5R cell line were found to transfer drug resistance to drug-sensitive HMPOS cells. The comparison of serum exosomes from dogs with a favorable disease-free interval [DFI] of >300 days, and dogs with <100 days DFI revealed a proteomic signature that could discriminate between the two cohorts with high accuracy. Furthermore, when the patient’s exosomes were compared to exosomes isolated from carboplatin resistant cell lines, several putative biomarkers were found to be shared.
Conclusions
The findings of this study highlight the significance of exosomes in the potential transfer of drug resistance, and the discovery of novel biomarkers for the development of liquid biopsies to better guide personalized chemotherapy treatment.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
This is a list of supplementary files associated with this preprint. Click to download.
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