Cytokines and Chemokines as Mediators of Prostate Cancer Metastasis

Abstract

The consequences of prostate cancer metastasis remain severe, with huge impact on the mortality and overall quality of life of affected patients. Despite the convoluted interplay and cross talk between various cell types and secreted factors in the metastatic process, cytokine and chemokines, along with their receptors and signaling axis, constitute important factors that help drive the sequence of events that lead to metastasis of prostate cancer. These proteins are involved in extracellular matrix remodeling, epithelial-mesenchymal-transition, angiogenesis, tumor invasion, premetastatic niche creation, extravasation, re-establishment of tumor cells in secondary organs as well as the remodeling of the metastatic tumor microenvironment. This review presents an overview of the main cytokines/chemokines, including IL-6, CXCL12, TGFβ, CXCL8, VEGF, RANKL, CCL2, CX3CL1, IL-1, IL-7, CXCL1, and CXCL16, that exert modulatory roles in prostate cancer metastasis. We also provide extensive description of their aberrant expression patterns in both advanced disease states and metastatic sites, as well as their functional involvement in the various stages of the prostate cancer metastatic process.

Dioscin Promotes Prostate Cancer Cell Apoptosis and Inhibits Cell Invasion by Increasing SHP1 Phosphorylation and Suppressing the Subsequent MAPK Signaling Pathway

“…IL-6 plays an important role in both the progression and treatment of PCa ( Hobisch et al., 2001 ; Johnson et al., 2018 ). IL-6 is a pleiotropic pro-inflammatory cytokine involved in the development of PCa and plays a role mediated through autocrine and paracrine mechanisms ( Adekoya and Richardson, 2020 ). Long-term application of IL-6 promotes PCa cell proliferation and thus can be used to establish in vitro models of advanced PCa ( Hobisch et al., 2001 ).…”

The Role of Inflammation in Breast and Prostate Cancer Metastasis to Bone

“…A high expression and activation of the CXCL12/CXCR4 axis can be found at preferred metastatic sites such as lymph nodes, liver, lungs, and the bone marrow associated with poor prognosis [ 195 , 203 , 204 , 205 ]. In bone metastases, CXCL12 and CXCR4 can be produced or expressed by a broad panel of cell types such as osteoblasts, osteocytes, CAFs, neutrophils, tumor cells, and adipocytes [ 47 , 113 , 206 , 207 , 208 , 209 ]. A high expression of CXCR4 in BrCa and PrCa tissue or tumor cells significantly correlates with distant lymph node, lung, and bone metastases, and increased aggressiveness [ 210 , 211 , 212 ].…”

“…In summary, inflammatory processes are a hub in cancer, being involved in virtually all steps of tumorigenesis, from initiation and promotion of primary tumor growth, to EMT, invasion, dissemination, and establishment of solid metastases [ 24 ]. In addition, inflammatory cytokines promote angiogenesis [ 47 ] and are associated with chemoresistance [ 48 ]. Unsurprisingly, an emerging number of preclinical and clinical studies are aimed at identifying the potential of anti-inflammatory agents targeting cytokines and chemokines, transcription factors, or inflammatory cells in patients with cancer (reviewed in [ 49 ]).…”

Increased Expressions of Matrix Metalloproteinases (MMPs) in Prostate Cancer Tissues of Men with Type 2 Diabetes

“…Several studies showed that EMT promotes metastasis in PCa [ 12 ]. In PCa, CC chemokine ligands (CCLs) are central regulators for inflammatory pathways [ 13 , 14 ]. The chemokine CCL2 was described to induce proliferation and migration of PCa cells [ 15 ].…”