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Article

Mast Cell-Derived SAMD14 Is a Novel Regulator of the Human Prostate Tumor Microenvironment

1
Monash Partners Comprehensive Cancer Consortium, Monash Biomedicine Discovery Institute Cancer Program, Prostate Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, Melbourne 3800, Australia
2
St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney 2010, Australia
3
Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney 2010, Australia
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Peter MacCallum Cancer Centre, Melbourne 3000, Australia
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Computational Cancer Biology Program, Peter MacCallum Cancer Centre, Melbourne 3000, Australia
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Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Melbourne 3010, Australia
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Monash Proteomics and Metabolomics Facility, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Melbourne 3800, Australia
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Melbourne Urological Research Alliance (MURAL), Monash Biomedicine Discovery Institute Cancer Program, Department of Anatomy and Developmental Biology, Monash University, Clayton, Melbourne 3800, Australia
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Monash Partners Comprehensive Cancer Consortium, Monash Biomedicine Discovery Institute Cancer Program, Prostate Cancer Research Group, Department of Physiology, Monash University, Clayton, Melbourne 3800, Australia
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School of Health and Wellbeing, University of Southern Queensland, Ipswich 4305, Australia
*
Authors to whom correspondence should be addressed.
Academic Editor: Jurgen Dittmer
Cancers 2021, 13(6), 1237; https://doi.org/10.3390/cancers13061237
Received: 18 February 2021 / Revised: 8 March 2021 / Accepted: 8 March 2021 / Published: 11 March 2021
(This article belongs to the Special Issue Microenvironment and Cancer Progression)
Mast cells are a type of immune cell that lives within organs and tissues of the body. When tumors develop in these organs, such as in prostate cancer, mast cells secrete multiple factors that can activate the tumor environment and help tumor cells to thrive. Here, we identify a gene called SAMD14 that is reduced in mast cells obtained from men with prostate cancer. We demonstrate that SAMD14 expression in mast cells can alter their secretions and promote the alignment of matrix fibers that cancer cells use to attach and move around on. By understanding how mast cells regulate their environment, we can reveal new directions of treatment that target the tumor environment as a whole, rather than just the tumor cells themselves.
Mast cells (MCs) are important cellular components of the tumor microenvironment and are significantly associated with poor patient outcomes in prostate cancer and other solid cancers. The promotion of tumor progression partly involves heterotypic interactions between MCs and cancer-associated fibroblasts (CAFs), which combine to potentiate a pro-tumor extracellular matrix and promote epithelial cell invasion and migration. Thus far, the interactions between MCs and CAFs remain poorly understood. To identify molecular changes that may alter resident MC function in the prostate tumor microenvironment, we profiled the transcriptome of human prostate MCs isolated from patient-matched non-tumor and tumor-associated regions of fresh radical prostatectomy tissue. Transcriptomic profiling revealed a distinct gene expression profile of MCs isolated from prostate tumor regions, including the downregulation of SAMD14, a putative tumor suppressor gene. Proteomic profiling revealed that overexpression of SAMD14 in HMC-1 altered the secretion of proteins associated with immune regulation and extracellular matrix processes. To assess MC biological function within a model of the prostate tumor microenvironment, HMC-1-SAMD14+ conditioned media was added to co-cultures of primary prostatic CAFs and prostate epithelium. HMC-1-SAMD14+ secretions were shown to reduce the deposition and alignment of matrix produced by CAFs and suppress pro-tumorigenic prostate epithelial morphology. Overall, our data present the first profile of human MCs derived from prostate cancer patient specimens and identifies MC-derived SAMD14 as an important mediator of MC phenotype and function within the prostate tumor microenvironment. View Full-Text
Keywords: prostate cancer; tumor microenvironment; mast cells; SAMD14; cancer-associated fibroblasts; extracellular matrix prostate cancer; tumor microenvironment; mast cells; SAMD14; cancer-associated fibroblasts; extracellular matrix
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MDPI and ACS Style

Teng, L.K.H.; Pereira, B.A.; Keerthikumar, S.; Huang, C.; Niranjan, B.; Lee, S.N.; Richards, M.; Schittenhelm, R.B.; Furic, L.; Goode, D.L.; Lawrence, M.G.; Taylor, R.A.; Ellem, S.J.; Risbridger, G.P.; Lister, N.L. Mast Cell-Derived SAMD14 Is a Novel Regulator of the Human Prostate Tumor Microenvironment. Cancers 2021, 13, 1237. https://doi.org/10.3390/cancers13061237

AMA Style

Teng LKH, Pereira BA, Keerthikumar S, Huang C, Niranjan B, Lee SN, Richards M, Schittenhelm RB, Furic L, Goode DL, Lawrence MG, Taylor RA, Ellem SJ, Risbridger GP, Lister NL. Mast Cell-Derived SAMD14 Is a Novel Regulator of the Human Prostate Tumor Microenvironment. Cancers. 2021; 13(6):1237. https://doi.org/10.3390/cancers13061237

Chicago/Turabian Style

Teng, Linda K.H., Brooke A. Pereira, Shivakumar Keerthikumar, Cheng Huang, Birunthi Niranjan, Sophie N. Lee, Michelle Richards, Ralf B. Schittenhelm, Luc Furic, David L. Goode, Mitchell G. Lawrence, Renea A. Taylor, Stuart J. Ellem, Gail P. Risbridger, and Natalie L. Lister. 2021. "Mast Cell-Derived SAMD14 Is a Novel Regulator of the Human Prostate Tumor Microenvironment" Cancers 13, no. 6: 1237. https://doi.org/10.3390/cancers13061237

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