Cyclin G2 in macrophages triggers CTL-mediated antitumor immunity and antiangiogenesis via interferon-gamma

Abstract

Background IFN-γ is a key mediator of tumor immunity that can induce macrophage polarization to suppress tumor growth. Cyclin G2 functions as a tumor suppressor in various cancer cells; however, its role in macrophages remains unclear. This study aimed to investigate the role and underlying mechanisms of cyclin G2 in macrophages in vitro and in vivo. Methods Mouse tumor models were used to determine the effect of cyclin G2 in macrophages on tumor growth in vivo following IFN-γ treatment. Immunohistochemistry staining, immunofluorescence staining and flow cytometry were used to evaluate the number of cytotoxic T lymphocytes (CTLs) and blood vessels in the mouse tumors. Moreover, the biological roles of cyclin G2 in macrophages with regard to CTL chemotaxis, cytotoxic function, and vascular endothelial cell tube formation were assessed using in vitro functional experiments. Immunoprecipitation (IP), real-time PCR, and enzyme-linked immunosorbent assays (ELISAs) were conducted to investigate the underlying mechanisms by which cyclin G2 regulates CTLs and vascular endothelial cells. Results We found that cyclin G2 expression was upregulated in macrophages after IFN-γ treatment. Upregulated cyclin G2 inhibited lung and colon cancer growth by increasing the secretion of its downstream effector CXCL9, which promoted CTL chemotaxis and suppressed vascular endothelial cell tube formation. Moreover, cyclin G2 increased CXCL9 mRNA levels by promoting STAT1 nuclear translocation. In addition, cyclin G2 promoted the activation of the STAT1 signaling pathway, which was dependent on PP2Ac. Conclusions Cyclin G2 is upregulated by IFN-γ in macrophages, promotes the secretion of CXCL9 to increase CTL chemotaxis and inhibit angiogenesis to suppress tumor growth. Our findings suggest that targeting cyclin G2 could benefit future immunotherapy.

In Situ Nanofiber Patch Boosts Postoperative Hepatocellular Carcinoma Immune Activation by Trimodal Combination Therapy

“…Western blot analysis in Figure c and Figure S11 revealed that the pro-apoptotic protein expression of Bax increased and the anti-apoptotic protein expression of Bcl-2 and Survivin decreased in the PAG+NIR group, leading to a decrease in the Bcl-2/Bax ratio. Meanwhile, MAPK/ERK and PI3K/Akt pathways were detected because they are the main downstream pathways of the VEGFR signaling pathway . As expected, the results indicated that the phosphorylation of ERK and Akt was downregulated after treatment with PAG+NIR.…”

“…Meanwhile, MAPK/ERK and PI3K/Akt pathways were detected because they are the main downstream pathways of the VEGFR signaling pathway. 42 As expected, the results indicated that the phosphorylation of ERK and Akt was downregulated after treatment with PAG+NIR. To further verify the mechanism of drug action, immunofluorescence staining of p-Akt and p-ERK was performed.…”

“…HCC is typically characterized by an abundance of blood vessels that provide the tumor with sufficient nutrients for growth . In this case, local cells, such as vascular endothelial cells (HUVECs) and tumor cells (H22), will overgrow wildly, eventually leading to deterioration.…”

“…HCC is typically characterized by an abundance of blood vessels that provide the tumor with sufficient nutrients for growth. 42 In this case, local cells, such as vascular endothelial cells (HUVECs) and tumor cells (H22), will overgrow wildly, eventually leading to deterioration. In view of the PTT and AL properties, patch-mediated vascular inhibition and antitumor effects were investigated at the cellular level.…”

Polystyrene microplastics mediate cell cycle arrest, apoptosis, and autophagy in the G2/M phase through ROS in grass carp kidney cells

“…23 G2 checkpoints, which prevent cells from undergoing mitosis when DNA damage is uncontrollable, may be a repair opportunity for self-healing. 39 Flow cytometry showed that PS-MPs increased the G2/M phase of CIK cells and decreased the G0/G1 phase proportion.…”