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

Linda K H Teng; 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; Natalie L Lister

doi:10.3390/cancers13061237

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

Cancers (Basel). 2021 Mar 11;13(6):1237. doi: 10.3390/cancers13061237.

Authors

Linda K H Teng¹, Brooke A Pereira^{2

3}, Shivakumar Keerthikumar^{4

5

6}, Cheng Huang⁷, Birunthi Niranjan¹, Sophie N Lee¹, Michelle Richards¹, Ralf B Schittenhelm⁷, Luc Furic^{1

4

6}, David L Goode^{4

5

6}, Mitchell G Lawrence^{1

4

6

8}, Renea A Taylor^{4

6

8

9}, Stuart J Ellem¹⁰, Gail P Risbridger^{1

4

6

8}, Natalie L Lister¹

Affiliations

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.
⁴ Peter MacCallum Cancer Centre, Melbourne 3000, Australia.
⁵ Computational Cancer Biology Program, Peter MacCallum Cancer Centre, Melbourne 3000, Australia.
⁶ Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Melbourne 3010, Australia.
⁷ Monash Proteomics and Metabolomics Facility, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Melbourne 3800, Australia.
⁸ Melbourne Urological Research Alliance (MURAL), Monash Biomedicine Discovery Institute Cancer Program, Department of Anatomy and Developmental Biology, Monash University, Clayton, Melbourne 3800, Australia.
⁹ Monash Partners Comprehensive Cancer Consortium, Monash Biomedicine Discovery Institute Cancer Program, Prostate Cancer Research Group, Department of Physiology, Monash University, Clayton, Melbourne 3800, Australia.
¹⁰ School of Health and Wellbeing, University of Southern Queensland, Ipswich 4305, Australia.

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: SAMD14; cancer-associated fibroblasts; extracellular matrix; mast cells; prostate cancer; tumor microenvironment.