Dynamic Landscape of Extracellular Vesicle-Associated Proteins Is Related to Treatment Response of Patients with Metastatic Breast Cancer

Breast cancer is the leading cause of cancer death in women. The majority of these deaths are due to disease metastasis, in which cancer cells disseminate to multiple organs and disrupt vital physiological functions. It is widely accepted that breast cancer cells secrete extracellular vesicles (EVs)...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Olivia Ruhen, Xinyu Qu, M. Fairuz B. Jamaluddin, Carlos Salomon, Aesha Gandhi, Michael Millward, Brett Nixon, Matthew D. Dun, Katie Meehan
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	metastatic breast cancer extracellular vesicles treatment response quantitative proteomics Chemical technology TP1-1185 Chemical engineering TP155-156
Acceso en línea:	https://doaj.org/article/596bb57a6da146349d6ad70a9bc8c080
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:596bb57a6da146349d6ad70a9bc8c080
record_format	dspace
spelling	oai:doaj.org-article:596bb57a6da146349d6ad70a9bc8c0802021-11-25T18:20:01ZDynamic Landscape of Extracellular Vesicle-Associated Proteins Is Related to Treatment Response of Patients with Metastatic Breast Cancer10.3390/membranes111108802077-0375https://doaj.org/article/596bb57a6da146349d6ad70a9bc8c0802021-11-01T00:00:00Zhttps://www.mdpi.com/2077-0375/11/11/880https://doaj.org/toc/2077-0375Breast cancer is the leading cause of cancer death in women. The majority of these deaths are due to disease metastasis, in which cancer cells disseminate to multiple organs and disrupt vital physiological functions. It is widely accepted that breast cancer cells secrete extracellular vesicles (EVs), which contain dynamic molecular cargo that act as versatile mediators of intercellular communication. Therefore, Evs. secreted by breast cancer cells could be involved in the development of metastatic disease and resistance to treatment. Moreover, changes in EV cargo could reflect the effects of therapy on their parent tumor cells. The aim of this feasibility study was to quantitatively profile the proteomes of Evs. isolated from blood samples taken from treatment sensitive and resistant metastatic breast cancer patients to identify proteins associated with responses. Three serial blood samples were collected from three patients with metastatic breast cancer receiving systemic therapy including a responder, a non-responder, and a mixed-responder. Evs. were isolated from plasma using size exclusion chromatography and their protein cargo was prepared for tandem mass tag (TMT)-labelling and quantitative analyses using two-dimensional high-performance liquid chromatography followed by tandem mass spectrometry. After filtering, we quantitatively identified 286 proteins with high confidence using a q value of 0.05. Of these, 149 were classified as EV associated candidate proteins and 137 as classical, high abundant plasma proteins. After comparing EV protein abundance between the responder and non-responder, we identified 35 proteins with unique de-regulated abundance patterns that was conserved at multiple time points. We propose that this proof-of-concept approach can be used to identify proteins which have potential as predictors of metastatic breast cancer response to treatment.Olivia RuhenXinyu QuM. Fairuz B. JamaluddinCarlos SalomonAesha GandhiMichael MillwardBrett NixonMatthew D. DunKatie MeehanMDPI AGarticlemetastatic breast cancerextracellular vesiclestreatment responsequantitative proteomicsChemical technologyTP1-1185Chemical engineeringTP155-156ENMembranes, Vol 11, Iss 880, p 880 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	metastatic breast cancer extracellular vesicles treatment response quantitative proteomics Chemical technology TP1-1185 Chemical engineering TP155-156
spellingShingle	metastatic breast cancer extracellular vesicles treatment response quantitative proteomics Chemical technology TP1-1185 Chemical engineering TP155-156 Olivia Ruhen Xinyu Qu M. Fairuz B. Jamaluddin Carlos Salomon Aesha Gandhi Michael Millward Brett Nixon Matthew D. Dun Katie Meehan Dynamic Landscape of Extracellular Vesicle-Associated Proteins Is Related to Treatment Response of Patients with Metastatic Breast Cancer
description	Breast cancer is the leading cause of cancer death in women. The majority of these deaths are due to disease metastasis, in which cancer cells disseminate to multiple organs and disrupt vital physiological functions. It is widely accepted that breast cancer cells secrete extracellular vesicles (EVs), which contain dynamic molecular cargo that act as versatile mediators of intercellular communication. Therefore, Evs. secreted by breast cancer cells could be involved in the development of metastatic disease and resistance to treatment. Moreover, changes in EV cargo could reflect the effects of therapy on their parent tumor cells. The aim of this feasibility study was to quantitatively profile the proteomes of Evs. isolated from blood samples taken from treatment sensitive and resistant metastatic breast cancer patients to identify proteins associated with responses. Three serial blood samples were collected from three patients with metastatic breast cancer receiving systemic therapy including a responder, a non-responder, and a mixed-responder. Evs. were isolated from plasma using size exclusion chromatography and their protein cargo was prepared for tandem mass tag (TMT)-labelling and quantitative analyses using two-dimensional high-performance liquid chromatography followed by tandem mass spectrometry. After filtering, we quantitatively identified 286 proteins with high confidence using a q value of 0.05. Of these, 149 were classified as EV associated candidate proteins and 137 as classical, high abundant plasma proteins. After comparing EV protein abundance between the responder and non-responder, we identified 35 proteins with unique de-regulated abundance patterns that was conserved at multiple time points. We propose that this proof-of-concept approach can be used to identify proteins which have potential as predictors of metastatic breast cancer response to treatment.
format	article
author	Olivia Ruhen Xinyu Qu M. Fairuz B. Jamaluddin Carlos Salomon Aesha Gandhi Michael Millward Brett Nixon Matthew D. Dun Katie Meehan
author_facet	Olivia Ruhen Xinyu Qu M. Fairuz B. Jamaluddin Carlos Salomon Aesha Gandhi Michael Millward Brett Nixon Matthew D. Dun Katie Meehan
author_sort	Olivia Ruhen
title	Dynamic Landscape of Extracellular Vesicle-Associated Proteins Is Related to Treatment Response of Patients with Metastatic Breast Cancer
title_short	Dynamic Landscape of Extracellular Vesicle-Associated Proteins Is Related to Treatment Response of Patients with Metastatic Breast Cancer
title_full	Dynamic Landscape of Extracellular Vesicle-Associated Proteins Is Related to Treatment Response of Patients with Metastatic Breast Cancer
title_fullStr	Dynamic Landscape of Extracellular Vesicle-Associated Proteins Is Related to Treatment Response of Patients with Metastatic Breast Cancer
title_full_unstemmed	Dynamic Landscape of Extracellular Vesicle-Associated Proteins Is Related to Treatment Response of Patients with Metastatic Breast Cancer
title_sort	dynamic landscape of extracellular vesicle-associated proteins is related to treatment response of patients with metastatic breast cancer
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/596bb57a6da146349d6ad70a9bc8c080
work_keys_str_mv	AT oliviaruhen dynamiclandscapeofextracellularvesicleassociatedproteinsisrelatedtotreatmentresponseofpatientswithmetastaticbreastcancer AT xinyuqu dynamiclandscapeofextracellularvesicleassociatedproteinsisrelatedtotreatmentresponseofpatientswithmetastaticbreastcancer AT mfairuzbjamaluddin dynamiclandscapeofextracellularvesicleassociatedproteinsisrelatedtotreatmentresponseofpatientswithmetastaticbreastcancer AT carlossalomon dynamiclandscapeofextracellularvesicleassociatedproteinsisrelatedtotreatmentresponseofpatientswithmetastaticbreastcancer AT aeshagandhi dynamiclandscapeofextracellularvesicleassociatedproteinsisrelatedtotreatmentresponseofpatientswithmetastaticbreastcancer AT michaelmillward dynamiclandscapeofextracellularvesicleassociatedproteinsisrelatedtotreatmentresponseofpatientswithmetastaticbreastcancer AT brettnixon dynamiclandscapeofextracellularvesicleassociatedproteinsisrelatedtotreatmentresponseofpatientswithmetastaticbreastcancer AT matthewddun dynamiclandscapeofextracellularvesicleassociatedproteinsisrelatedtotreatmentresponseofpatientswithmetastaticbreastcancer AT katiemeehan dynamiclandscapeofextracellularvesicleassociatedproteinsisrelatedtotreatmentresponseofpatientswithmetastaticbreastcancer
_version_	1718411320854839296

Dynamic Landscape of Extracellular Vesicle-Associated Proteins Is Related to Treatment Response of Patients with Metastatic Breast Cancer

Ejemplares similares