1. Monocytic and granulocytic myeloid derived suppressor cells differentially regulate spatiotemporal tumour plasticity during metastatic cascade
- Author
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John K. Cowell, Khaled A. Hassan, Hasan Korkaya, Maria Ouzounova, Ali S. Arbab, Raziye Piranlioglu, Gang Zhou, Muthusamy Thangaraju, Daniela Marasco, Abdeljabar El Andaloussi, Ahmed Chadli, Iskander Asm, Eunmi Lee, Mehmet F. Demirci, Ravindra Kolhe, Ouzounova, Maria, Lee, Eunmi, Piranlioglu, Raziye, El Andaloussi, Abdeljabar, Kolhe, Ravindra, Demirci, Mehmet F, Marasco, Daniela, Asm, Iskander, Chadli, Ahmed, Hassan, Khaled A, Thangaraju, Muthusamy, Zhou, Gang, Arbab, Ali S, Cowell, John K, Korkaya, Hasan, Augusta University, and University System of Georgia (USG)
- Subjects
0301 basic medicine ,[SDV]Life Sciences [q-bio] ,Science ,Cell ,General Physics and Astronomy ,Biology ,Monocytes ,Article ,General Biochemistry, Genetics and Molecular Biology ,Metastasis ,Transcriptome ,03 medical and health sciences ,Lung metastasis, tumor cell plasticity, SOCS proteins ,Cell Line, Tumor ,Neoplasms ,Cell Plasticity ,medicine ,Animals ,Humans ,Neoplasm Metastasis ,Cells, Cultured ,ComputingMilieux_MISCELLANEOUS ,Cell Proliferation ,Mice, Inbred BALB C ,Multidisciplinary ,Cell growth ,Gene Expression Profiling ,Myeloid-Derived Suppressor Cells ,digestive, oral, and skin physiology ,Mammary Neoplasms, Experimental ,General Chemistry ,Gene signature ,medicine.disease ,Phenotype ,3. Good health ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Immunology ,Myeloid-derived Suppressor Cell ,Cancer research ,Female ,Granulocytes - 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., Myeloid-derived suppressive cells (MDSCs) promote metastasis. Here, the authors show that the monocytic MDSCs subset promotes epithelial to mesenchymal transition at the primary site while the granulocytic subset promotes the reverse transition at the metastatic site enabling dynamic tumour cells plasticity.
- Published
- 2017