ABSTRACT
PURPOSE: Gastric cancer is a gastrointestinal malignancy with high mortality and poor prognosis, and the molecular mechanism of gastric tumorigenesis remains unclear. TRIM44 has been reported to be involved in tumor development. However, the role of TRIM44 in tumor immunity is largely unknown. METHODS: We analyzed TRIM44 expression in clinical gastric cancer tissues and normal tissues by using western blot, quantitative real-time PCR and bioinformatics analyses. We further investigated the involvement of TRIM44 in tumor immunity in vivo and found that it was dependent on extracellular matrix remodeling. We detected the interaction between TRIM44 and LOXL2 by using immunofluorescence staining and coimmunoprecipitation assays. We observed that TRIM44 mediates the stability of LOXL2 by ubiquitination assays. RESULTS: TRIM44 expression is high and is correlated with T-cell infiltration in gastric cancer. TRIM44 inhibits gastric tumorigenicity by regulating T-cell-mediated antitumor immunity and modulating the protein level of LOXL2. Mechanistically, TRIM44 directly binds to LOXL2 and affects the stability of LOXL2 to change extracellular matrix remodeling and influence tumor immunity. CONCLUSION: These findings demonstrate that TRIM44 regulates the stability of LOXL2 to remodel the tumor extracellular matrix to modulate tumor immunity in gastric cancer and that the TRIM44/LOXL2 complex is a promising biomarker for gastric cancer prognosis and might be a novel immunotherapy target.
Subject(s)
Extracellular Matrix , Stomach Neoplasms , Tumor Microenvironment , Humans , Amino Acid Oxidoreductases/genetics , Amino Acid Oxidoreductases/metabolism , Biomarkers , Cell Line, Tumor , Extracellular Matrix/metabolism , Gene Expression Regulation, Neoplastic , Intracellular Signaling Peptides and Proteins/metabolism , Stomach Neoplasms/genetics , Stomach Neoplasms/immunology , Tripartite Motif Proteins/metabolism , Tumor Microenvironment/immunologyABSTRACT
A series of poly(lactide)/poly(butylene adipate-co-terephthalate) (PLA/PBAT) composites containing different types of multi-walled carbon nanotubes (CNTs) such as hydroxyl and carboxyl-functionalized CNTs were fabricated using the melt blending method. The multifunctional epoxy oligomer (ADR) was selected as a chain extender in order to enhance the compatibility between PBAT and PLA. It was revealed that the addition of ADR could induce CNTs-OH to locate at the PLA/PBAT interface. But the inhibition effect of CNTs-COOH on chain extension reaction in PLA/PBAT blend system led to a decrease in the interaction force between PLA and PBAT owing to the high efficiency of the reaction between CNTs-COOH and ADR. The ε' of PLA/PBAT/4CNTs-OH composite was greater than that of PLA/PBAT/4CNTs-COOH composite because of the strong interaction between fillers and polymer matrix in PLA/PBAT/4CNTs-OH composite. The PLA/PBAT/4CNTs-OH composite showed a high ε' (24.9) and a low tan δ (0.23), respectively. The adjacent CNTs-OH could act as assemble microcapacitors electrodes and the polymer acted as a dielectric to, which greatly increased the interfacial polarization. The PLA/PBAT/4CNTs-OH composite has excellent mechanical and dielectric properties.
