Role of Chemokines and Cytokines in Prostate Cancer Skeletal Metastasis

Abstract

Purpose of review: Once prostate cancer (PCa) bone metastases develop, the prognosis dramatically declines. The precise mechanisms regulating bone metastasis remain elusive. This review will explore recent findings related to cytokines and chemokines in the process of bone metastases.

Recent findings: We discuss the role of cytokines in tumor growth, invasion, bone remodelling and angiogenesis and immune regulation in PCa skeletal metastases. Major advances in our understanding focus on immune evasion, immune checkpoint blockade, tumor-associated macrophages (TAMs), CAR-T cells, cytokine regulation of matrix metalloproteinases, cytokines including IL-10, IL-27, Interferon-γ, prostate transmembrane protein androgen induced 1 (Pmepa1), and regulation of RUNX2 transcription in supporting survival and growth of disseminated tumor cells (DTCs) and metastases development. The review highlights the complexity of cytokine actions in PCa bone metastases, suggesting potential therapeutic targets to disrupt interactions between cancer cells and their microenvironment.

Keywords: Chemokines; Cytokines; Disseminated tumor cells; Prostate cancer; Skeletal metastases.

Figure 1:. The roles of cytokines and chemokines in prostate cancer (PCa) bone metastasis

Studies regarding the roles of cytokines and chemokines in the context of PCa bone metastasis has yielded important insights into the crosstalk between bone metastatic PCa cells and bone marrow microenvironment. Cytokines and chemokines, produced by either PCa cells or bone marrow microenvironment, are known to regulate phenomena that are crucial for PCa bone metastatic development/progression. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and IL-8 induce neovascularization in the bone to support PCa growth in the bone. Moreover, IL-10 and TGF-β induce immunosuppressive effects and IL-4 and IL-13 promote M2 polarization of tumor-associate macrophages (TAM). Understanding of underlying mechanisms could help develop targeted therapies to disrupt the crosstalk between bone metastatic PCa cells and bone marrow microenvironment. Graphics adapted from Smart Servier Medical Art (https://smart.servier.com/).