Monocytic and granulocytic myeloid derived suppressor cells differentially regulate spatiotemporal tumour plasticity during metastatic cascade

Maria Ouzounova, Eunmi Lee, Raziye Piranlioglu, Abdeljabar El Andaloussi, Ravindra Bharat Kolhe, Mehmet F. Demirci, Daniela Marasco, Iskander Asm, Ahmed Chadli, Khaled A. Hassan, Muthusamy Thangaraju, Gang Zhou, Ali Syed Arbab, John Kenneth Cowell, Hasan Korkaya

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

It is widely accepted that dynamic and reversible tumour cell plasticity is required for metastasis, however, in vivo steps and molecular mechanisms are poorly elucidated. We demonstrate here that monocytic (mMDSC) and granulocytic (gMDSC) subsets of myeloid-derived suppressor cells infiltrate in the primary tumour and distant organs with different time kinetics and regulate spatiotemporal tumour plasticity. Using co-culture experiments and mouse transcriptome analyses in syngeneic mouse models, we provide evidence that tumour-infiltrated mMDSCs facilitate tumour cell dissemination from the primary site by inducing EMT/CSC phenotype. In contrast, pulmonary gMDSC infiltrates support the metastatic growth by reverting EMT/CSC phenotype and promoting tumour cell proliferation. Furthermore, lung-derived gMDSCs isolated from tumour-bearing animals enhance metastatic growth of already disseminated tumour cells. MDSC-induced â € metastatic gene signature' derived from murine syngeneic model predicts poor patient survival in the majority of human solid tumours. Thus spatiotemporal MDSC infiltration may have clinical implications in tumour progression.

Original languageEnglish (US)
Article number14979
JournalNature Communications
Volume8
DOIs
StatePublished - Apr 6 2017

Fingerprint

suppressors
plastic properties
Plasticity
Tumors
cascades
tumors
cells
Neoplasms
phenotype
Cells
mice
Bearings (structural)
Myeloid-Derived Suppressor Cells
Phenotype
Lung
Cell proliferation
Gene Expression Profiling
metastasis
infiltration
Growth

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Monocytic and granulocytic myeloid derived suppressor cells differentially regulate spatiotemporal tumour plasticity during metastatic cascade. / Ouzounova, Maria; Lee, Eunmi; Piranlioglu, Raziye; El Andaloussi, Abdeljabar; Kolhe, Ravindra Bharat; Demirci, Mehmet F.; Marasco, Daniela; Asm, Iskander; Chadli, Ahmed; Hassan, Khaled A.; Thangaraju, Muthusamy; Zhou, Gang; Arbab, Ali Syed; Cowell, John Kenneth; Korkaya, Hasan.

In: Nature Communications, Vol. 8, 14979, 06.04.2017.

Research output: Contribution to journalArticle

@article{7cf56c84e2f040af9645203f01900578,
title = "Monocytic and granulocytic myeloid derived suppressor cells differentially regulate spatiotemporal tumour plasticity during metastatic cascade",
abstract = "It is widely accepted that dynamic and reversible tumour cell plasticity is required for metastasis, however, in vivo steps and molecular mechanisms are poorly elucidated. We demonstrate here that monocytic (mMDSC) and granulocytic (gMDSC) subsets of myeloid-derived suppressor cells infiltrate in the primary tumour and distant organs with different time kinetics and regulate spatiotemporal tumour plasticity. Using co-culture experiments and mouse transcriptome analyses in syngeneic mouse models, we provide evidence that tumour-infiltrated mMDSCs facilitate tumour cell dissemination from the primary site by inducing EMT/CSC phenotype. In contrast, pulmonary gMDSC infiltrates support the metastatic growth by reverting EMT/CSC phenotype and promoting tumour cell proliferation. Furthermore, lung-derived gMDSCs isolated from tumour-bearing animals enhance metastatic growth of already disseminated tumour cells. MDSC-induced {\^a} € metastatic gene signature' derived from murine syngeneic model predicts poor patient survival in the majority of human solid tumours. Thus spatiotemporal MDSC infiltration may have clinical implications in tumour progression.",
author = "Maria Ouzounova and Eunmi Lee and Raziye Piranlioglu and {El Andaloussi}, Abdeljabar and Kolhe, {Ravindra Bharat} and Demirci, {Mehmet F.} and Daniela Marasco and Iskander Asm and Ahmed Chadli and Hassan, {Khaled A.} and Muthusamy Thangaraju and Gang Zhou and Arbab, {Ali Syed} and Cowell, {John Kenneth} and Hasan Korkaya",
year = "2017",
month = "4",
day = "6",
doi = "10.1038/ncomms14979",
language = "English (US)",
volume = "8",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Monocytic and granulocytic myeloid derived suppressor cells differentially regulate spatiotemporal tumour plasticity during metastatic cascade

AU - Ouzounova, Maria

AU - Lee, Eunmi

AU - Piranlioglu, Raziye

AU - El Andaloussi, Abdeljabar

AU - Kolhe, Ravindra Bharat

AU - Demirci, Mehmet F.

AU - Marasco, Daniela

AU - Asm, Iskander

AU - Chadli, Ahmed

AU - Hassan, Khaled A.

AU - Thangaraju, Muthusamy

AU - Zhou, Gang

AU - Arbab, Ali Syed

AU - Cowell, John Kenneth

AU - Korkaya, Hasan

PY - 2017/4/6

Y1 - 2017/4/6

N2 - It is widely accepted that dynamic and reversible tumour cell plasticity is required for metastasis, however, in vivo steps and molecular mechanisms are poorly elucidated. We demonstrate here that monocytic (mMDSC) and granulocytic (gMDSC) subsets of myeloid-derived suppressor cells infiltrate in the primary tumour and distant organs with different time kinetics and regulate spatiotemporal tumour plasticity. Using co-culture experiments and mouse transcriptome analyses in syngeneic mouse models, we provide evidence that tumour-infiltrated mMDSCs facilitate tumour cell dissemination from the primary site by inducing EMT/CSC phenotype. In contrast, pulmonary gMDSC infiltrates support the metastatic growth by reverting EMT/CSC phenotype and promoting tumour cell proliferation. Furthermore, lung-derived gMDSCs isolated from tumour-bearing animals enhance metastatic growth of already disseminated tumour cells. MDSC-induced â € metastatic gene signature' derived from murine syngeneic model predicts poor patient survival in the majority of human solid tumours. Thus spatiotemporal MDSC infiltration may have clinical implications in tumour progression.

AB - It is widely accepted that dynamic and reversible tumour cell plasticity is required for metastasis, however, in vivo steps and molecular mechanisms are poorly elucidated. We demonstrate here that monocytic (mMDSC) and granulocytic (gMDSC) subsets of myeloid-derived suppressor cells infiltrate in the primary tumour and distant organs with different time kinetics and regulate spatiotemporal tumour plasticity. Using co-culture experiments and mouse transcriptome analyses in syngeneic mouse models, we provide evidence that tumour-infiltrated mMDSCs facilitate tumour cell dissemination from the primary site by inducing EMT/CSC phenotype. In contrast, pulmonary gMDSC infiltrates support the metastatic growth by reverting EMT/CSC phenotype and promoting tumour cell proliferation. Furthermore, lung-derived gMDSCs isolated from tumour-bearing animals enhance metastatic growth of already disseminated tumour cells. MDSC-induced â € metastatic gene signature' derived from murine syngeneic model predicts poor patient survival in the majority of human solid tumours. Thus spatiotemporal MDSC infiltration may have clinical implications in tumour progression.

UR - http://www.scopus.com/inward/record.url?scp=85017186697&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85017186697&partnerID=8YFLogxK

U2 - 10.1038/ncomms14979

DO - 10.1038/ncomms14979

M3 - Article

C2 - 28382931

AN - SCOPUS:85017186697

VL - 8

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 14979

ER -