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 '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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Georgia Cancer Center, Augusta University, Augusta, Georgia 30912, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Ouzounova
authors.affiliation: Department of Biochemistry and Molecular Biology, Georgia Cancer Center, Augusta University, Augusta, Georgia 30912, USA.
authors.forename: Eunmi
authors.initials: E
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Molecular Biology, Georgia Cancer Center, Augusta University, Augusta, Georgia 30912, USA.
authors.forename: Raziye
authors.initials: R
authors.lastname: Piranlioglu
authors.affiliation: Department of Biochemistry and Molecular Biology, Georgia Cancer Center, Augusta University, Augusta, Georgia 30912, USA.
authors.forename: Abdeljabar
authors.initials: A
authors.lastname: El Andaloussi
authors.affiliation: Department of Biochemistry and Molecular Biology, Georgia Cancer Center, Augusta University, Augusta, Georgia 30912, USA.
authors.forename: Ravindra
authors.initials: R
authors.lastname: Kolhe
authors.affiliation: Department of Biochemistry and Molecular Biology, Georgia Cancer Center, Augusta University, Augusta, Georgia 30912, USA.
authors.forename: Mehmet F
authors.initials: MF
authors.lastname: Demirci
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Naples 80138, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Marasco
authors.affiliation: Department of Biochemistry and Molecular Biology, Georgia Cancer Center, Augusta University, Augusta, Georgia 30912, USA.
authors.forename: Iskander
authors.initials: I
authors.lastname: Asm
authors.affiliation: Department of Biochemistry and Molecular Biology, Georgia Cancer Center, Augusta University, Augusta, Georgia 30912, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Chadli
authors.affiliation: Department of Internal Medicine, Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Khaled A
authors.initials: KA
authors.lastname: Hassan
authors.affiliation: Department of Biochemistry and Molecular Biology, Georgia Cancer Center, Augusta University, Augusta, Georgia 30912, USA.
authors.forename: Muthusamy
authors.initials: M
authors.lastname: Thangaraju
authors.affiliation: Department of Biochemistry and Molecular Biology, Georgia Cancer Center, Augusta University, Augusta, Georgia 30912, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry and Molecular Biology, Georgia Cancer Center, Augusta University, Augusta, Georgia 30912, USA.
authors.forename: Ali S
authors.initials: AS
authors.lastname: Arbab
authors.affiliation: Department of Biochemistry and Molecular Biology, Georgia Cancer Center, Augusta University, Augusta, Georgia 30912, USA.
authors.forename: John K
authors.initials: JK
authors.lastname: Cowell
authors.affiliation: Department of Biochemistry and Molecular Biology, Georgia Cancer Center, Augusta University, Augusta, Georgia 30912, USA.
authors.forename: Hasan
authors.identifier: 0000-0002-0719-5862
authors.initials: H
authors.lastname: Korkaya
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006098:Granulocytes / Q000378:metabolism*; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism*; D000072737:Myeloid-Derived Suppressor Cells / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology