Mast Cell‐Derived SAMD14 is a Novel Regulator of the Human Prostate Tumor Microenvironment
Article
Article Title | Mast Cell‐Derived SAMD14 is a Novel Regulator of the Human |
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ERA Journal ID | 200262 |
Article Category | Article |
Authors | Teng, 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 Title | Cancers |
Journal Citation | 13 (6), pp. 1-25 |
Article Number | 1237 |
Number of Pages | 25 |
Year | 2021 |
Place of Publication | Switzerland |
ISSN | 2072-6694 |
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. |
Keywords | prostate cancer; tumor microenvironment; mast cells; SAMD14; cancer‐associated fibroblasts;extracellular matrix |
ANZSRC Field of Research 2020 | 321199. Oncology and carcinogenesis not elsewhere classified |
321101. Cancer cell biology | |
320214. Nephrology and urology | |
Byline Affiliations | Monash University |
University of New South Wales | |
University of Melbourne | |
School of Health and Wellbeing | |
Institution of Origin | University of Southern Queensland |
https://research.usq.edu.au/item/q6454/mast-cell-derived-samd14-is-a-novel-regulator-of-the-human-prostate-tumor-microenvironment
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