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

Article


Teng, Linda K. H., Pereira, Brooke A., Keerthikumar, Shivakumar, Huang, Cheng, Niranjan, Birunthi, Lee, Sophie N., Richards, Michelle, Schittenhelm, Ralf B., Furic, Luc, Goode, David L., Lawrence, Mitchell G., Taylor, Renea A., Ellem, Stuart J., 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), pp. 1-25. https://doi.org/10.3390/cancers13061237
Article Title

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

ERA Journal ID200262
Article CategoryArticle
AuthorsTeng, Linda K. H. (Author), Pereira, Brooke A. (Author), Keerthikumar, Shivakumar (Author), Huang, Cheng (Author), Niranjan, Birunthi (Author), Lee, Sophie N. (Author), Richards, Michelle (Author), Schittenhelm, Ralf B. (Author), Furic, Luc (Author), Goode, David L. (Author), Lawrence, Mitchell G. (Author), Taylor, Renea A. (Author), Ellem, Stuart J. (Author), Risbridger, Gail P. (Author) and Lister, Natalie L. (Author)
Journal TitleCancers
Journal Citation13 (6), pp. 1-25
Article Number1237
Number of Pages25
Year2021
Place of PublicationSwitzerland
ISSN2072-6694
Digital Object Identifier (DOI)https://doi.org/10.3390/cancers13061237
Web Address (URL)https://www.mdpi.com/2072-6694/13/6/1237
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.

Keywordsprostate cancer; tumor microenvironment; mast cells; SAMD14; cancer‐associated fibroblasts;extracellular matrix
ANZSRC Field of Research 2020321199. Oncology and carcinogenesis not elsewhere classified
321101. Cancer cell biology
320214. Nephrology and urology
Byline AffiliationsMonash University
University of New South Wales
University of Melbourne
School of Health and Wellbeing
Institution of OriginUniversity of Southern Queensland
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