Paradoxical Roles of Tumour Necrosis Factor-Alpha in Prostate Cancer Biology

Table 1

Summary of potential protumour and antitumour roles of TNF in PCaPCa.

Protumour	Reference
Involvement in the initiation of castrate resistant PCa by inducing hypersensitivity to androgen (LNCaP cells)	[12]
Induces neutrophil production of myeloperoxidase, which generates carcinogenic reactive oxygen species (ROS) and hypochlorous acid	[27]
Induces in vitro chemotaxis and proliferation of endothelial cells at low doses	[29, 30]
Upregulates E-, P-, and L-selectin ligands on LNCaP cells, which may facilitate extravasation to bloodstream	[31]
Increases expression of MMP-9, fibronectin and decreases E-Cadherin by PC-3 cells	[32]
Involvement in epithelial-mesenchymal plasticity via Snail	[32]
May stimulate tumour proliferation and reduce apoptosis via PGE2	[33]
Antitumour	Reference
Induces regression of normal prostate	[22]
Inhibits in vitro and in vivo angiogenesis at high doses	[30, 34]
Induces apoptosis of LNCaP cells	[35, 36]
Stimulates antitumour immunity by enhancing the generation and proliferation of cytotoxic T cells (CTL); Also prevents TGF-β-mediated inhibition of CTL generation	[7, 37, 38]
Induces production of other cytokines (e.g., IL-1, IL-6, IL-8, and IFN-γ) and cytotoxic factors (e.g., NO and ROS) by macrophages and NK cells	[7]
Protects dendritic cells from tumour-induced apoptosis	[39]