2. Academic Validation
  3. Stromal-derived MAOB promotes prostate cancer growth and progression

Stromal-derived MAOB promotes prostate cancer growth and progression

  • Sci Adv. 2024 Feb 9;10(6):eadi4935. doi: 10.1126/sciadv.adi4935.
Tianjie Pu 1,  Jing Wang 1,  Jing Wei 1,  Alan Zeng 2,  Jinglong Zhang 1,  Jingrui Chen 1,  Lijuan Yin 3,  Jingjing Li 1,  Tzu-Ping Lin 4 5,  Jonathan Melamed 6,  Eva Corey 7,  Allen C Gao 8,  Boyang Jason Wu 1
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA 99202, USA.
  • 2 Undergraduate Programs, University of Washington, Seattle, WA 98195, USA.
  • 3 Uro-Oncology Research Program, Samuel Oschin Comprehensive Cancer Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • 4 Department of Urology, Taipei Veterans General Hospital, Taipei 11217, Taiwan, Republic of China.
  • 5 Department of Urology, School of Medicine and Shu-Tien Urological Research Center, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan, Republic of China.
  • 6 Department of Pathology, Grossman School of Medicine, New York University, New York, NY 10016, USA.
  • 7 Department of Urology, University of Washington, Seattle, WA 98195, USA.
  • 8 Department of Urologic Surgery, University of California, Davis, Sacramento, CA 95817, USA.
PMID: 38335292 DOI: 10.1126/sciadv.adi4935
Abstract

Prostate Cancer (PC) develops in a microenvironment where the stromal cells modulate adjacent tumor growth and progression. Here, we demonstrated elevated levels of Monoamine Oxidase B (MAOB), a mitochondrial Enzyme that degrades biogenic and dietary monoamines, in human PC stroma, which was associated with poor clinical outcomes of PC patients. Knockdown or overexpression of MAOB in human prostate stromal fibroblasts indicated that MAOB promotes cocultured PC cell proliferation, migration, and invasion and co-inoculated prostate tumor growth in mice. Mechanistically, MAOB induces a reactive stroma with activated marker expression, increased extracellular matrix remodeling, and acquisition of a protumorigenic phenotype through enhanced production of Reactive Oxygen Species. Moreover, MAOB transcriptionally activates CXCL12 through Twist1 synergizing with TGFβ1-dependent Smads in prostate stroma, which stimulates tumor-expressed CXCR4-Src/JNK signaling in a paracrine manner. Pharmacological inhibition of stromal MAOB restricted PC xenograft growth in mice. Collectively, these findings characterize the contribution of MAOB to PC and suggest MAOB as a potential stroma-based therapeutic target.

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