miRNa signature in small extracellular vesicles and their association with platinum resistance and cancer recurrence in ovarian cancer

Alharbi, Mona; Sharma, Shayna; Guanzon, Dominic; Lai, Andrew; Zúñiga, Felipe; Shiddiky, Muhammad J. A.; Yamauchi, Yusuke; Salas-Burgos, Alexis; He, Yaowu; Pejović, Tanja; Winters, Carmen; Morgan, Terry K.; Perrin, Lewis; Hooper, John D.; Salomón, Carlos

doi:10.1016/j.nano.2020.102207

Cited by 42 publications

(47 citation statements)

References 49 publications

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“…There are immense efforts to identify the mechanisms associated with chemotherapy resistance, to improve treatment outcomes, and reduce adverse effects associated with these treatments. Recent studies revealed the critical role of exosomes in chemotherapy resistance, which was linked to their microRNA cargo; however, the role of other exosomal components have not been thoroughly investigated [ 25 , 26 ]. In the current study we have identified proteins associated with carboplatin drug resistance generated in vitro and demonstrated the acquisition of this resistance by sensitive cells following exposure to exosomes from drug-resistant cells.…”

Section: Discussionmentioning

confidence: 99%

Exosomal proteomic signatures correlate with drug resistance and carboplatin treatment outcome in a spontaneous model of canine osteosarcoma

et al. 2021

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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.

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Section: Discussionmentioning

confidence: 99%

Exosomal proteomic signatures correlate with drug resistance and carboplatin treatment outcome in a spontaneous model of canine osteosarcoma

et al. 2021

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“…There are immense efforts to identify the mechanisms associated with chemotherapy resistance, to improve treatment outcomes, and reduce adverse effects associated with these treatments. Recent studies revealed the critical role of exosomes in chemotherapy resistance, which was linked to their microRNA cargo; however, the role of other exosomal components have not been thoroughly investigated [28,29]. In the current study we have identi ed proteins associated with carboplatin drug resistance generated in vitro and demonstrated the acquisition of this resistance by sensitive cells following exposure to exosomes from drug-resistant cells.…”

Section: Discussionmentioning

confidence: 72%

Exosomal Proteomic Signatures Correlate With Drug Resistance and Carboplatin Treatment Outcome in a Spontaneous Model of Canine Osteosarcoma

Weinman

Ramsey

Leeper

et al. 2021

Preprint

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BackgroundOsteosarcoma 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. MethodsIn 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. ResultsBoth 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. ConclusionsThe 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.

show abstract

“…These exosomal miRNAs could play a role of chemotherapy resistance in OC by upregulating detoxification metabolic pathways and DNA repair mechanisms. 112 Asare-Werehene et al demonstrated increased expression and secretion of plasma gelsolin (pGSN) in chemotherapy-resistant OC cells compared with the chemically sensitive counterparts. pGSN is secreted and carried by exosomes (ex-pGSN) to upregulate HIF1α-induced pGSN expression via an autocrine pathway in chemotherapy-resistant OC cells and induces cisplatin resistance in other chemosensitive OC cells.…”

Section: Exosomes Induce Drug Resistance In Female Reproductive Systementioning

confidence: 99%

<p>The Role of Exosomes in the Female Reproductive System and Breast Cancers</p>

Bai

Guo

et al. 2020

OTT

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miRNa signature in small extracellular vesicles and their association with platinum resistance and cancer recurrence in ovarian cancer

Cited by 42 publications

References 49 publications

Exosomal proteomic signatures correlate with drug resistance and carboplatin treatment outcome in a spontaneous model of canine osteosarcoma

Exosomal proteomic signatures correlate with drug resistance and carboplatin treatment outcome in a spontaneous model of canine osteosarcoma

Exosomal Proteomic Signatures Correlate With Drug Resistance and Carboplatin Treatment Outcome in a Spontaneous Model of Canine Osteosarcoma

<p>The Role of Exosomes in the Female Reproductive System and Breast Cancers</p>

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