Sex steroids in the tumor microenvironment and prostate cancer progression

Prostate cancer is uniquely dependent on androgens. Despite years of research on the relationship between androgens and prostate cancer, many questions remain as to the biological effects of androgens and other sex steroids during prostate cancer progression. This article reviews the clinical and basic research on the influence of sex steroids such as androgens, estrogens and progesterone within the prostate tumor microenvironment on the progression of prostate cancer. We review clinical studies to date evaluating serum sex steroids as prognostic biomarkers and discuss their respective biological effects within the prostate tumor microenvironment. We also review the link between genomic alterations and sex steroid levels within prostate tumors. Finally, we highlight the links between sex steroid levels and the function of the immune system within the tumor microenvironment. As the context of treatment of lethal prostate cancer evolves over time, an understanding of this underlying biology remains central to developing optimal treatment approaches.

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Regulation of prostate cancer progression by the tumor microenvironment

Cancer Letters ◽

10.1016/j.canlet.2015.12.022 ◽

2016 ◽

Vol 380 (1) ◽

pp. 340-348 ◽

Cited By ~ 67

Author(s):

Stephen L. Shiao ◽

Gina Chia-Yi Chu ◽

Leland W.K. Chung

Keyword(s):

Prostate Cancer ◽

Tumor Microenvironment ◽

Cancer Progression ◽

Prostate Cancer Progression

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Main Inflammatory Cells and Potentials of Anti-Inflammatory Agents in Prostate Cancer

Cancers ◽

10.3390/cancers11081153 ◽

2019 ◽

Vol 11 (8) ◽

pp. 1153 ◽

Cited By ~ 12

Author(s):

Takuji Hayashi ◽

Kazutoshi Fujita ◽

Makoto Matsushita ◽

Norio Nonomura

Keyword(s):

Prostate Cancer ◽

Cancer Progression ◽

Immune Cells ◽

Acquired Resistance ◽

Suppressor Cells ◽

Basic Research ◽

Inflammatory Cells ◽

Intercellular Signaling ◽

Prostate Cancer Progression ◽

Anti Inflammatory

Prostate cancer is the most common type of cancer and the leading cause of cancer deaths among men in many countries. Preventing progression is a major concern for prostate cancer patients on active surveillance, patients with recurrence after radical therapies, and patients who acquired resistance to systemic therapies. Inflammation, which is induced by various factors such as infection, microbiome, obesity, and a high-fat diet, is the major etiology in the development of prostate cancer. Inflammatory cells play important roles in tumor progression. Various immune cells including tumor-associated neutrophils, tumor-infiltrating macrophages, myeloid-derived suppressor cells, and mast cells promote prostate cancer via various intercellular signaling. Further basic studies examining the relationship between the inflammatory process and prostate cancer progression are warranted. Interventions by medications and diets to control systemic and/or local inflammation might be effective therapies for prostate cancer progression. Epidemiological investigations and basic research using human immune cells or mouse models have revealed that non-steroidal anti-inflammatory drugs, metformin, statins, soy isoflavones, and other diets are potential interventions for preventing progression of prostate cancer by suppressing inflammation. It is essential to evaluate appropriate indications and doses of each drug and diet.

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Prostate tumor OVerexpressed-1 (PTOV1) down-regulates HES1 and HEY1 notch targets genes and promotes prostate cancer progression

Molecular Cancer ◽

10.1186/1476-4598-13-74 ◽

2014 ◽

Vol 13 (1) ◽

pp. 74 ◽

Cited By ~ 20

Author(s):

Lide Alaña ◽

Marta Sesé ◽

Verónica Cánovas ◽

Yolanda Punyal ◽

Yolanda Fernández ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Progression ◽

Prostate Tumor ◽

Prostate Cancer Progression

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Increased AKT Activity Contributes to Prostate Cancer Progression by Dramatically Accelerating Prostate Tumor Growth and Diminishing p27Kip1Expression

Journal of Biological Chemistry ◽

10.1074/jbc.m003145200 ◽

2000 ◽

Vol 275 (32) ◽

pp. 24500-24505 ◽

Cited By ~ 257

Author(s):

Jeremy R. Graff ◽

Bruce W. Konicek ◽

Ann M. McNulty ◽

Zejing Wang ◽

Keith Houck ◽

...

Keyword(s):

Prostate Cancer ◽

Tumor Growth ◽

Cancer Progression ◽

Prostate Tumor ◽

Prostate Cancer Progression

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Arginine and Arginases Modulate Metabolism, Tumor Microenvironment and Prostate Cancer Progression

Nutrients ◽

10.3390/nu13124503 ◽

2021 ◽

Vol 13 (12) ◽

pp. 4503

Author(s):

Andreia Matos ◽

Marcos Carvalho ◽

Manuel Bicho ◽

Ricardo Ribeiro

Keyword(s):

Prostate Cancer ◽

Tumor Microenvironment ◽

Cancer Progression ◽

Urea Cycle ◽

Suppressor Cells ◽

Myeloid Derived Suppressor Cells ◽

Prostate Cancer Progression ◽

Arginine Metabolism ◽

Arginine Deprivation ◽

The Impact

Arginine availability and activation of arginine-related pathways at cancer sites have profound effects on the tumor microenvironment, far beyond their well-known role in the hepatic urea cycle. Arginine metabolism impacts not only malignant cells but also the surrounding immune cells behavior, modulating growth, survival, and immunosurveillance mechanisms, either through an arginase-mediated effect on polyamines and proline synthesis, or by the arginine/nitric oxide pathway in tumor cells, antitumor T-cells, myeloid-derived suppressor cells, and macrophages. This review presents evidence concerning the impact of arginine metabolism and arginase activity in the prostate cancer microenvironment, highlighting the recent advances in immunotherapy, which might be relevant for prostate cancer. Even though further research is required, arginine deprivation may represent a novel antimetabolite strategy for the treatment of arginine-dependent prostate cancer.

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