Mast Cell‐Derived SAMD14 is a Novel Regulator of the Human Prostate Tumor Microenvironment

Teng, Linda K. H. and Pereira, Brooke A. and Keerthikumar, Shivakumar and Huang, Cheng and Niranjan, Birunthi and Lee, Sophie N. and Richards, Michelle and Schittenhelm, Ralf B. and Furic, Luc and Goode, David L. and Lawrence, Mitchell G. and Taylor, Renea A. and Ellem, Stuart J. and Risbridger, Gail P. and Lister, Natalie L. (2021) Mast Cell‐Derived SAMD14 is a Novel Regulator of the Human Prostate Tumor Microenvironment. Cancers, 13 (6):1237. pp. 1-25. ISSN 2072-6694

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Abstract

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.


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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Faculty/School / Institute/Centre: Current - Faculty of Health, Engineering and Sciences - School of Health and Wellbeing (1 Jan 2015 -)
Faculty/School / Institute/Centre: Current - Faculty of Health, Engineering and Sciences - School of Health and Wellbeing (1 Jan 2015 -)
Date Deposited: 16 Mar 2021 01:09
Last Modified: 23 Jun 2021 07:39
Uncontrolled Keywords: prostate cancer; tumor microenvironment; mast cells; SAMD14; cancer‐associated fibroblasts;extracellular matrix
Fields of Research (2008): 11 Medical and Health Sciences > 1112 Oncology and Carcinogenesis > 111201 Cancer Cell Biology
11 Medical and Health Sciences > 1103 Clinical Sciences > 110312 Nephrology and Urology
11 Medical and Health Sciences > 1112 Oncology and Carcinogenesis > 111299 Oncology and Carcinogenesis not elsewhere classified
Fields of Research (2020): 32 BIOMEDICAL AND CLINICAL SCIENCES > 3211 Oncology and carcinogenesis > 321199 Oncology and carcinogenesis not elsewhere classified
32 BIOMEDICAL AND CLINICAL SCIENCES > 3211 Oncology and carcinogenesis > 321101 Cancer cell biology
32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320214 Nephrology and urology
Socio-Economic Objectives (2008): C Society > 92 Health > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920119 Urogenital System and Disorders
C Society > 92 Health > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920114 Reproductive System and Disorders
C Society > 92 Health > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920102 Cancer and Related Disorders
Socio-Economic Objectives (2020): 20 HEALTH > 2005 Specific population health (excl. Indigenous health) > 200504 Men's health
20 HEALTH > 2001 Clinical health > 200199 Clinical health not elsewhere classified
20 HEALTH > 2099 Other health > 209999 Other health not elsewhere classified
Identification Number or DOI: https://doi.org/10.3390/cancers13061237
URI: http://eprints.usq.edu.au/id/eprint/41565

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