Preferential transfer of mitochondria from endothelial to cancer cells through tunneling nanotubes modulates chemoresistance

Jennifer Pasquier, Bella S. Guerrouahen, Hamda Al Thawadi, Pegah Ghiabi, Mahtab Maleki, Nadine Abu-Kaoud, Arthur Jacob, Massoud Mirshahi, Ludovic Galas, Shahin Rafii, Frank Le Foll, Arash Rafii Tabrizi

Research output: Contribution to journalArticle

154 Citations (Scopus)

Abstract

Our vision of cancer has changed during the past decades. Indeed tumors are now perceived as complex entities where tumoral and stromal components interact closely. Among the different elements of tumor stroma the cellular component play a primordial role. Bone Marrow derived mesenchymal cells (MSCs) are attracted to tumor sites and support tumor growth. Endothelial cells (ECs) play a major role in angiogenesis. While the literature documents many aspects of the cross talk between stromal and cancer cells, the role of direct hetero-cellular contact is not clearly established. Recently, Tunneling nanotubes (TnTs) have been shown to support cell-to-cell transfers of plasma membrane components, cytosolic molecules and organelles within cell lines. Herein, we have investigated the formation of heterocellular TnTs between stromal (MSCs and ECs) and cancer cells. We demonstrate that TnTs occur between different cancer cells, stromal cells and cancer-stromal cell lines. We showed that TnTs-like structure occurred in 3D anchorage independent spheroids and also in tumor explant cultures. In our culture condition, TnTs formation occurred after large membrane adhesion. We showed that intercellular transfers of cytoplasmic content occurred similarly between cancer cells and MSCs or ECs, but we highlighted that the exchange of mitochondria occurred preferentially between endothelial cells and cancer cells. We illustrated that the cancer cells acquiring mitochondria displayed chemoresistance. Our results illustrate the perfusion-independent role of the endothelium by showing a direct endothelial to cancer cell mitochondrial exchange associated to phenotypic modulation. This supports another role of the endothelium in the constitution of the metastatic niche.

Original languageEnglish
Article number94
JournalJournal of Translational Medicine
Volume11
Issue number1
DOIs
Publication statusPublished - 10 Apr 2013

Fingerprint

Nanotubes
Mitochondria
Cells
Endothelial cells
Tumors
Neoplasms
Endothelial Cells
Stromal Cells
Endothelium
Cell membranes
Cell Line
Bone
Adhesion
Modulation
Constitution and Bylaws
Membranes
Mesenchymal Stromal Cells
Organelles
Molecules

Keywords

  • Cancer cells
  • Chemoresistance
  • Endothelial cells
  • Intercellular transfer
  • Tunneling nanotubes

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Preferential transfer of mitochondria from endothelial to cancer cells through tunneling nanotubes modulates chemoresistance. / Pasquier, Jennifer; Guerrouahen, Bella S.; Al Thawadi, Hamda; Ghiabi, Pegah; Maleki, Mahtab; Abu-Kaoud, Nadine; Jacob, Arthur; Mirshahi, Massoud; Galas, Ludovic; Rafii, Shahin; Le Foll, Frank; Tabrizi, Arash Rafii.

In: Journal of Translational Medicine, Vol. 11, No. 1, 94, 10.04.2013.

Research output: Contribution to journalArticle

Pasquier, Jennifer ; Guerrouahen, Bella S. ; Al Thawadi, Hamda ; Ghiabi, Pegah ; Maleki, Mahtab ; Abu-Kaoud, Nadine ; Jacob, Arthur ; Mirshahi, Massoud ; Galas, Ludovic ; Rafii, Shahin ; Le Foll, Frank ; Tabrizi, Arash Rafii. / Preferential transfer of mitochondria from endothelial to cancer cells through tunneling nanotubes modulates chemoresistance. In: Journal of Translational Medicine. 2013 ; Vol. 11, No. 1.
@article{510d189c70a148df8e0f67150caabd3e,
title = "Preferential transfer of mitochondria from endothelial to cancer cells through tunneling nanotubes modulates chemoresistance",
abstract = "Our vision of cancer has changed during the past decades. Indeed tumors are now perceived as complex entities where tumoral and stromal components interact closely. Among the different elements of tumor stroma the cellular component play a primordial role. Bone Marrow derived mesenchymal cells (MSCs) are attracted to tumor sites and support tumor growth. Endothelial cells (ECs) play a major role in angiogenesis. While the literature documents many aspects of the cross talk between stromal and cancer cells, the role of direct hetero-cellular contact is not clearly established. Recently, Tunneling nanotubes (TnTs) have been shown to support cell-to-cell transfers of plasma membrane components, cytosolic molecules and organelles within cell lines. Herein, we have investigated the formation of heterocellular TnTs between stromal (MSCs and ECs) and cancer cells. We demonstrate that TnTs occur between different cancer cells, stromal cells and cancer-stromal cell lines. We showed that TnTs-like structure occurred in 3D anchorage independent spheroids and also in tumor explant cultures. In our culture condition, TnTs formation occurred after large membrane adhesion. We showed that intercellular transfers of cytoplasmic content occurred similarly between cancer cells and MSCs or ECs, but we highlighted that the exchange of mitochondria occurred preferentially between endothelial cells and cancer cells. We illustrated that the cancer cells acquiring mitochondria displayed chemoresistance. Our results illustrate the perfusion-independent role of the endothelium by showing a direct endothelial to cancer cell mitochondrial exchange associated to phenotypic modulation. This supports another role of the endothelium in the constitution of the metastatic niche.",
keywords = "Cancer cells, Chemoresistance, Endothelial cells, Intercellular transfer, Tunneling nanotubes",
author = "Jennifer Pasquier and Guerrouahen, {Bella S.} and {Al Thawadi}, Hamda and Pegah Ghiabi and Mahtab Maleki and Nadine Abu-Kaoud and Arthur Jacob and Massoud Mirshahi and Ludovic Galas and Shahin Rafii and {Le Foll}, Frank and Tabrizi, {Arash Rafii}",
year = "2013",
month = "4",
day = "10",
doi = "10.1186/1479-5876-11-94",
language = "English",
volume = "11",
journal = "Journal of Translational Medicine",
issn = "1479-5876",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Preferential transfer of mitochondria from endothelial to cancer cells through tunneling nanotubes modulates chemoresistance

AU - Pasquier, Jennifer

AU - Guerrouahen, Bella S.

AU - Al Thawadi, Hamda

AU - Ghiabi, Pegah

AU - Maleki, Mahtab

AU - Abu-Kaoud, Nadine

AU - Jacob, Arthur

AU - Mirshahi, Massoud

AU - Galas, Ludovic

AU - Rafii, Shahin

AU - Le Foll, Frank

AU - Tabrizi, Arash Rafii

PY - 2013/4/10

Y1 - 2013/4/10

N2 - Our vision of cancer has changed during the past decades. Indeed tumors are now perceived as complex entities where tumoral and stromal components interact closely. Among the different elements of tumor stroma the cellular component play a primordial role. Bone Marrow derived mesenchymal cells (MSCs) are attracted to tumor sites and support tumor growth. Endothelial cells (ECs) play a major role in angiogenesis. While the literature documents many aspects of the cross talk between stromal and cancer cells, the role of direct hetero-cellular contact is not clearly established. Recently, Tunneling nanotubes (TnTs) have been shown to support cell-to-cell transfers of plasma membrane components, cytosolic molecules and organelles within cell lines. Herein, we have investigated the formation of heterocellular TnTs between stromal (MSCs and ECs) and cancer cells. We demonstrate that TnTs occur between different cancer cells, stromal cells and cancer-stromal cell lines. We showed that TnTs-like structure occurred in 3D anchorage independent spheroids and also in tumor explant cultures. In our culture condition, TnTs formation occurred after large membrane adhesion. We showed that intercellular transfers of cytoplasmic content occurred similarly between cancer cells and MSCs or ECs, but we highlighted that the exchange of mitochondria occurred preferentially between endothelial cells and cancer cells. We illustrated that the cancer cells acquiring mitochondria displayed chemoresistance. Our results illustrate the perfusion-independent role of the endothelium by showing a direct endothelial to cancer cell mitochondrial exchange associated to phenotypic modulation. This supports another role of the endothelium in the constitution of the metastatic niche.

AB - Our vision of cancer has changed during the past decades. Indeed tumors are now perceived as complex entities where tumoral and stromal components interact closely. Among the different elements of tumor stroma the cellular component play a primordial role. Bone Marrow derived mesenchymal cells (MSCs) are attracted to tumor sites and support tumor growth. Endothelial cells (ECs) play a major role in angiogenesis. While the literature documents many aspects of the cross talk between stromal and cancer cells, the role of direct hetero-cellular contact is not clearly established. Recently, Tunneling nanotubes (TnTs) have been shown to support cell-to-cell transfers of plasma membrane components, cytosolic molecules and organelles within cell lines. Herein, we have investigated the formation of heterocellular TnTs between stromal (MSCs and ECs) and cancer cells. We demonstrate that TnTs occur between different cancer cells, stromal cells and cancer-stromal cell lines. We showed that TnTs-like structure occurred in 3D anchorage independent spheroids and also in tumor explant cultures. In our culture condition, TnTs formation occurred after large membrane adhesion. We showed that intercellular transfers of cytoplasmic content occurred similarly between cancer cells and MSCs or ECs, but we highlighted that the exchange of mitochondria occurred preferentially between endothelial cells and cancer cells. We illustrated that the cancer cells acquiring mitochondria displayed chemoresistance. Our results illustrate the perfusion-independent role of the endothelium by showing a direct endothelial to cancer cell mitochondrial exchange associated to phenotypic modulation. This supports another role of the endothelium in the constitution of the metastatic niche.

KW - Cancer cells

KW - Chemoresistance

KW - Endothelial cells

KW - Intercellular transfer

KW - Tunneling nanotubes

UR - http://www.scopus.com/inward/record.url?scp=84875932682&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875932682&partnerID=8YFLogxK

U2 - 10.1186/1479-5876-11-94

DO - 10.1186/1479-5876-11-94

M3 - Article

C2 - 23574623

AN - SCOPUS:84875932682

VL - 11

JO - Journal of Translational Medicine

JF - Journal of Translational Medicine

SN - 1479-5876

IS - 1

M1 - 94

ER -