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Microparticles mediated cross-talk between tumoral and endothelial cells promote the constitution of a pro-metastatic vascular niche through Arf6 up regulation.

Pasquier J, Thawadi HA, Ghiabi P, Abu-Kaoud N, Maleki M, Guerrouahen BS, Vidal F, Courderc B, Ferron G, Martinez A, Al Sulaiti H, Gupta R, Rafii S, Rafii A - Cancer Microenviron (2014)

Bottom Line: Our data show that MPs from mesenchymal-like cell lines (MDA-MB231, SKOV3 and APOCC) were able to promote an activation of endothelial cells through Akt phosphorylation, compared to MPs from epithelial-like cell lines (OVCAR3 and MCF7).The endothelial activation was associated to increased Arf6 expression and MPs secretion.Such cross-talk may play a role in perfusion independent role of the endothelium.

View Article: PubMed Central - PubMed

Affiliation: Stem Cell and Microenvironment Laboratory, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar.

ABSTRACT
The tumor stroma plays an essential role in tumor growth, resistance to therapy and occurrence of metastatic phenotype. Tumor vessels have been considered as passive conducts for nutrients but several studies have demonstrated secretion of pro-tumoral factors by endothelial cells. The failure of anti-angiogenic therapies to meet expectations raised by pre-clinical studies prompt us to better study the cross-talk between endothelial and cancer cells. Here, we hypothesized that tumor cells and the endothelium secrete bio-active microparticles (MPs) participating to a functional cross-talk. We characterized the cancer cells MPs, using breast and ovarian cancer cell lines (MCF7, MDA-MB231, SKOV3, OVCAR3 and a primary cell lines, APOCC). Our data show that MPs from mesenchymal-like cell lines (MDA-MB231, SKOV3 and APOCC) were able to promote an activation of endothelial cells through Akt phosphorylation, compared to MPs from epithelial-like cell lines (OVCAR3 and MCF7). The MPs from mesenchymal-like cells contained increased angiogenic molecules including PDGF, IL8 and angiogenin. The endothelial activation was associated to increased Arf6 expression and MPs secretion. Endothelial activation functionalized an MP dependent pro-tumoral vascular niche promoting cancer cells proliferation, invasiveness, stem cell phenotype and chemoresistance. MPs from cancer and endothelial cells displayed phenotypic heterogeneity, and participated to a functional cross-talk where endothelial activation by cancer MPs resulted in increased secretion of EC-MPs sustaining tumor cells. Such cross-talk may play a role in perfusion independent role of the endothelium.

No MeSH data available.


Related in: MedlinePlus

Cancer cells microparticles induce vascular activation. a Schematic representation of the experimental design. b HUVECs were plated and counted every 2 days in presence or not of MPs from CCs. Only MPs from MDA and Skov3 were able to sustain proliferation of HUVECs. c Wound closure assay was performed for HUVECs in presence or absence of CCs-MPs. Only MPs from MDA and Skov3 enhanced HUVECs motility. d HUVECs were plated on matrigel layer in presence or not of CC-MPs. Tube formation were quantified at different time. Only MPs from MDA and Skov3 were able to improve the number of tube and their viability. The bottom panel grave representative picture of the tubes at 4 and 6 h after plating. Scale bar: 500 μm
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Fig2: Cancer cells microparticles induce vascular activation. a Schematic representation of the experimental design. b HUVECs were plated and counted every 2 days in presence or not of MPs from CCs. Only MPs from MDA and Skov3 were able to sustain proliferation of HUVECs. c Wound closure assay was performed for HUVECs in presence or absence of CCs-MPs. Only MPs from MDA and Skov3 enhanced HUVECs motility. d HUVECs were plated on matrigel layer in presence or not of CC-MPs. Tube formation were quantified at different time. Only MPs from MDA and Skov3 were able to improve the number of tube and their viability. The bottom panel grave representative picture of the tubes at 4 and 6 h after plating. Scale bar: 500 μm

Mentions: To investigate the functional effect of MPs on endothelial cells, HUVECs were incubated with MPs from MCF7 and OVCAR3, referred as E-MPs (Epithelial-MPs), or MPs from MDA, SKOV3 and APOCC, referred as M-MPs (Mesenchymal-MPs), Fig. 2a.Fig. 2


Microparticles mediated cross-talk between tumoral and endothelial cells promote the constitution of a pro-metastatic vascular niche through Arf6 up regulation.

Pasquier J, Thawadi HA, Ghiabi P, Abu-Kaoud N, Maleki M, Guerrouahen BS, Vidal F, Courderc B, Ferron G, Martinez A, Al Sulaiti H, Gupta R, Rafii S, Rafii A - Cancer Microenviron (2014)

Cancer cells microparticles induce vascular activation. a Schematic representation of the experimental design. b HUVECs were plated and counted every 2 days in presence or not of MPs from CCs. Only MPs from MDA and Skov3 were able to sustain proliferation of HUVECs. c Wound closure assay was performed for HUVECs in presence or absence of CCs-MPs. Only MPs from MDA and Skov3 enhanced HUVECs motility. d HUVECs were plated on matrigel layer in presence or not of CC-MPs. Tube formation were quantified at different time. Only MPs from MDA and Skov3 were able to improve the number of tube and their viability. The bottom panel grave representative picture of the tubes at 4 and 6 h after plating. Scale bar: 500 μm
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4150875&req=5

Fig2: Cancer cells microparticles induce vascular activation. a Schematic representation of the experimental design. b HUVECs were plated and counted every 2 days in presence or not of MPs from CCs. Only MPs from MDA and Skov3 were able to sustain proliferation of HUVECs. c Wound closure assay was performed for HUVECs in presence or absence of CCs-MPs. Only MPs from MDA and Skov3 enhanced HUVECs motility. d HUVECs were plated on matrigel layer in presence or not of CC-MPs. Tube formation were quantified at different time. Only MPs from MDA and Skov3 were able to improve the number of tube and their viability. The bottom panel grave representative picture of the tubes at 4 and 6 h after plating. Scale bar: 500 μm
Mentions: To investigate the functional effect of MPs on endothelial cells, HUVECs were incubated with MPs from MCF7 and OVCAR3, referred as E-MPs (Epithelial-MPs), or MPs from MDA, SKOV3 and APOCC, referred as M-MPs (Mesenchymal-MPs), Fig. 2a.Fig. 2

Bottom Line: Our data show that MPs from mesenchymal-like cell lines (MDA-MB231, SKOV3 and APOCC) were able to promote an activation of endothelial cells through Akt phosphorylation, compared to MPs from epithelial-like cell lines (OVCAR3 and MCF7).The endothelial activation was associated to increased Arf6 expression and MPs secretion.Such cross-talk may play a role in perfusion independent role of the endothelium.

View Article: PubMed Central - PubMed

Affiliation: Stem Cell and Microenvironment Laboratory, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar.

ABSTRACT
The tumor stroma plays an essential role in tumor growth, resistance to therapy and occurrence of metastatic phenotype. Tumor vessels have been considered as passive conducts for nutrients but several studies have demonstrated secretion of pro-tumoral factors by endothelial cells. The failure of anti-angiogenic therapies to meet expectations raised by pre-clinical studies prompt us to better study the cross-talk between endothelial and cancer cells. Here, we hypothesized that tumor cells and the endothelium secrete bio-active microparticles (MPs) participating to a functional cross-talk. We characterized the cancer cells MPs, using breast and ovarian cancer cell lines (MCF7, MDA-MB231, SKOV3, OVCAR3 and a primary cell lines, APOCC). Our data show that MPs from mesenchymal-like cell lines (MDA-MB231, SKOV3 and APOCC) were able to promote an activation of endothelial cells through Akt phosphorylation, compared to MPs from epithelial-like cell lines (OVCAR3 and MCF7). The MPs from mesenchymal-like cells contained increased angiogenic molecules including PDGF, IL8 and angiogenin. The endothelial activation was associated to increased Arf6 expression and MPs secretion. Endothelial activation functionalized an MP dependent pro-tumoral vascular niche promoting cancer cells proliferation, invasiveness, stem cell phenotype and chemoresistance. MPs from cancer and endothelial cells displayed phenotypic heterogeneity, and participated to a functional cross-talk where endothelial activation by cancer MPs resulted in increased secretion of EC-MPs sustaining tumor cells. Such cross-talk may play a role in perfusion independent role of the endothelium.

No MeSH data available.


Related in: MedlinePlus