Extracellular vesicles with altered tetraspanin CD9 and CD151 levels confer increased prostate cell motility and invasion

Joshua S. Brzozowski, Danielle R. Bond, Helen Jankowski, Belinda J. Goldie, Rachel Burchell, Crystal Naudin, Nathan D. Smith, Christopher J. Scarlett, Martin R. Larsen, Matthew D. Dun, Kathryn A. Skelding, Judith Weidenhofer*

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Resumé

To facilitate intercellular communication, cells release nano-sized, extracellular vesicles (EVs) to transfer biological cargo to both local and distant sites. EVs are enriched in tetraspanins, two of which (CD9 and CD151) have altered expression patterns in many solid tumours, including prostate cancer, as they advance toward metastasis. We aimed to determine whether EVs from prostate cells with altered CD9 and CD151 expression could influence cellular behaviour and increase the metastatic capabilities of non-tumourigenic prostate cells. EVs were isolated by ultrafiltration and characterised for their tetraspanin expression and size distribution. iTRAQ was used to identify differences between RWPE1 and tetraspanin-modified RWPE1 EV proteomes, showing an enrichment in protein degradation pathways. Addition of EVs from RWPE1 cells with reduced CD9 or increased CD151 abundance resulted in increased invasion of RWPE1 cells, and increased migration in the case of high CD151 abundance. We have been able to show that alteration of CD9 and CD151 on prostate cells alters the proteome of their resultant EVs, and that these EVs can enhance the migratory and invasive capabilities of a non-tumourigenic prostate cellular population. This work suggests that cellular tetraspanin levels can alter EVs, potentially acting as a driver of metastasis in prostate cancer.

OriginalsprogEngelsk
Artikelnummer8822
TidsskriftScientific Reports
Vol/bind8
Antal sider13
ISSN2045-2322
DOI
StatusUdgivet - 11. jun. 2018

Fingeraftryk

Cell Movement
Prostate
Proteome
Prostatic Neoplasms
Tetraspanins
Ultrafiltration
Cell Communication
Proteolysis
Population
Neoplasms

Citer dette

Brzozowski, J. S., Bond, D. R., Jankowski, H., Goldie, B. J., Burchell, R., Naudin, C., ... Weidenhofer, J. (2018). Extracellular vesicles with altered tetraspanin CD9 and CD151 levels confer increased prostate cell motility and invasion. Scientific Reports, 8, [8822]. https://doi.org/10.1038/s41598-018-27180-z
Brzozowski, Joshua S. ; Bond, Danielle R. ; Jankowski, Helen ; Goldie, Belinda J. ; Burchell, Rachel ; Naudin, Crystal ; Smith, Nathan D. ; Scarlett, Christopher J. ; Larsen, Martin R. ; Dun, Matthew D. ; Skelding, Kathryn A. ; Weidenhofer, Judith. / Extracellular vesicles with altered tetraspanin CD9 and CD151 levels confer increased prostate cell motility and invasion. I: Scientific Reports. 2018 ; Bind 8.
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title = "Extracellular vesicles with altered tetraspanin CD9 and CD151 levels confer increased prostate cell motility and invasion",
abstract = "To facilitate intercellular communication, cells release nano-sized, extracellular vesicles (EVs) to transfer biological cargo to both local and distant sites. EVs are enriched in tetraspanins, two of which (CD9 and CD151) have altered expression patterns in many solid tumours, including prostate cancer, as they advance toward metastasis. We aimed to determine whether EVs from prostate cells with altered CD9 and CD151 expression could influence cellular behaviour and increase the metastatic capabilities of non-tumourigenic prostate cells. EVs were isolated by ultrafiltration and characterised for their tetraspanin expression and size distribution. iTRAQ was used to identify differences between RWPE1 and tetraspanin-modified RWPE1 EV proteomes, showing an enrichment in protein degradation pathways. Addition of EVs from RWPE1 cells with reduced CD9 or increased CD151 abundance resulted in increased invasion of RWPE1 cells, and increased migration in the case of high CD151 abundance. We have been able to show that alteration of CD9 and CD151 on prostate cells alters the proteome of their resultant EVs, and that these EVs can enhance the migratory and invasive capabilities of a non-tumourigenic prostate cellular population. This work suggests that cellular tetraspanin levels can alter EVs, potentially acting as a driver of metastasis in prostate cancer.",
author = "Brzozowski, {Joshua S.} and Bond, {Danielle R.} and Helen Jankowski and Goldie, {Belinda J.} and Rachel Burchell and Crystal Naudin and Smith, {Nathan D.} and Scarlett, {Christopher J.} and Larsen, {Martin R.} and Dun, {Matthew D.} and Skelding, {Kathryn A.} and Judith Weidenhofer",
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Brzozowski, JS, Bond, DR, Jankowski, H, Goldie, BJ, Burchell, R, Naudin, C, Smith, ND, Scarlett, CJ, Larsen, MR, Dun, MD, Skelding, KA & Weidenhofer, J 2018, 'Extracellular vesicles with altered tetraspanin CD9 and CD151 levels confer increased prostate cell motility and invasion', Scientific Reports, bind 8, 8822. https://doi.org/10.1038/s41598-018-27180-z

Extracellular vesicles with altered tetraspanin CD9 and CD151 levels confer increased prostate cell motility and invasion. / Brzozowski, Joshua S.; Bond, Danielle R.; Jankowski, Helen; Goldie, Belinda J.; Burchell, Rachel; Naudin, Crystal; Smith, Nathan D.; Scarlett, Christopher J.; Larsen, Martin R.; Dun, Matthew D.; Skelding, Kathryn A.; Weidenhofer, Judith.

I: Scientific Reports, Bind 8, 8822, 11.06.2018.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Extracellular vesicles with altered tetraspanin CD9 and CD151 levels confer increased prostate cell motility and invasion

AU - Brzozowski, Joshua S.

AU - Bond, Danielle R.

AU - Jankowski, Helen

AU - Goldie, Belinda J.

AU - Burchell, Rachel

AU - Naudin, Crystal

AU - Smith, Nathan D.

AU - Scarlett, Christopher J.

AU - Larsen, Martin R.

AU - Dun, Matthew D.

AU - Skelding, Kathryn A.

AU - Weidenhofer, Judith

PY - 2018/6/11

Y1 - 2018/6/11

N2 - To facilitate intercellular communication, cells release nano-sized, extracellular vesicles (EVs) to transfer biological cargo to both local and distant sites. EVs are enriched in tetraspanins, two of which (CD9 and CD151) have altered expression patterns in many solid tumours, including prostate cancer, as they advance toward metastasis. We aimed to determine whether EVs from prostate cells with altered CD9 and CD151 expression could influence cellular behaviour and increase the metastatic capabilities of non-tumourigenic prostate cells. EVs were isolated by ultrafiltration and characterised for their tetraspanin expression and size distribution. iTRAQ was used to identify differences between RWPE1 and tetraspanin-modified RWPE1 EV proteomes, showing an enrichment in protein degradation pathways. Addition of EVs from RWPE1 cells with reduced CD9 or increased CD151 abundance resulted in increased invasion of RWPE1 cells, and increased migration in the case of high CD151 abundance. We have been able to show that alteration of CD9 and CD151 on prostate cells alters the proteome of their resultant EVs, and that these EVs can enhance the migratory and invasive capabilities of a non-tumourigenic prostate cellular population. This work suggests that cellular tetraspanin levels can alter EVs, potentially acting as a driver of metastasis in prostate cancer.

AB - To facilitate intercellular communication, cells release nano-sized, extracellular vesicles (EVs) to transfer biological cargo to both local and distant sites. EVs are enriched in tetraspanins, two of which (CD9 and CD151) have altered expression patterns in many solid tumours, including prostate cancer, as they advance toward metastasis. We aimed to determine whether EVs from prostate cells with altered CD9 and CD151 expression could influence cellular behaviour and increase the metastatic capabilities of non-tumourigenic prostate cells. EVs were isolated by ultrafiltration and characterised for their tetraspanin expression and size distribution. iTRAQ was used to identify differences between RWPE1 and tetraspanin-modified RWPE1 EV proteomes, showing an enrichment in protein degradation pathways. Addition of EVs from RWPE1 cells with reduced CD9 or increased CD151 abundance resulted in increased invasion of RWPE1 cells, and increased migration in the case of high CD151 abundance. We have been able to show that alteration of CD9 and CD151 on prostate cells alters the proteome of their resultant EVs, and that these EVs can enhance the migratory and invasive capabilities of a non-tumourigenic prostate cellular population. This work suggests that cellular tetraspanin levels can alter EVs, potentially acting as a driver of metastasis in prostate cancer.

U2 - 10.1038/s41598-018-27180-z

DO - 10.1038/s41598-018-27180-z

M3 - Journal article

C2 - 29891991

AN - SCOPUS:85048424178

VL - 8

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 8822

ER -