Aberrant LYZ expression in tumor cells serves as the potential biomarker and target for HCC and promotes tumor progression via csGRP78.

Hepatocellular carcinoma (HCC) takes the predominant malignancy of hepatocytes with bleak outcomes owing to high heterogeneity among patients. Personalized treatments based on molecular profiles will better improve patients' prognosis. Lysozyme (LYZ), a secretory protein with antibacterial function generally expressed in monocytes/macrophages, has been observed for the prognostic implications in different types of tumors. However, studies about the explicit applicative scenarios and mechanisms for tumor progression are still quite limited, especially for HCC. Here, based on the proteomic molecular classification data of early-stage HCC, we revealed that the LYZ level was elevated significantly in the most malignant HCC subtype and could serve as an independent prognostic predictor for HCC patients. Molecular profiles of LYZ-high HCCs were typical of those for the most malignant HCC subtype, with impaired metabolism, along with promoted proliferation and metastasis characteristics. Further studies demonstrated that LYZ tended to be aberrantly expressed in poorly differentiated HCC cells, which was regulated by STAT3 activation. LYZ promoted HCC proliferation and migration in both autocrine and paracrine manners independent of the muramidase activity through the activation of downstream protumoral signaling pathways via cell surface GRP78. Subcutaneous and orthotopic xenograft tumor models indicated that targeting LYZ inhibited HCC growth markedly in NOD/SCID mice. These results propose LYZ as a prognostic biomarker and therapeutic target for the subclass of HCC with an aggressive phenotype.

Knockdown of ferritin heavy chain (FTH) inhibits the migration of prostate cancer through reducing S100A4, S100A2, and S100P expression.

BACKGROUND: Ferritin plays a key role in the development of prostate cancer (PCa). Our earlier studies showed that the knockdown of ferritin heavy chain (FTH) suppressed the migration and invasion of the prostate cancer cell line (PC3). However, the mechanisms behind FTH in the cell migration regulation of PCa have not been thoroughly investigated. METHODS: Isobaric tags for relative and absolute quantitation (iTRAQ) proteomics was used to analyze the protein expression in PC3 cells with FTH knockdown by small interfering RNAs and negative control cells. We subsequently ranked the differentially expressed proteins according to the change in expression. We further performed Gene Ontology (GO) analysis for the changing-expression protein. Finally, Western blot analysis was performed to determine the expression of the target protein. RESULTS: Compared with the negative group, 420 proteins were downregulated, including proteins S100A4, S100P, and S100A2, while the expression of 442 protein was elevated in FTH-silencing PC3 cells (P<0.05, fold change >1.2). The mass spectrometry results showing decreased expression of protein S100A4, S100P, and S100A2 in the cells were further validated by Western blot (P<0.05). Levels of protein S100A4, S100A2, and S100P were reduced in FTH-silencing PC3 cells (P<0.05, fold change >1.6). CONCLUSIONS: The downregulation of FTH expression reduced the level of protein S100A4, S100A2, and S100P, which all play a key role in the migration and invasion of tumor cells. Therefore, it is reasonable to assume that there are correlations between the expression of the S100A4, S100A2, and S100P genes with FTH. Based on this research, FTH may be a new biomarker for the diagnosis of PCa.

[Imiquimod combined with dendritic cell vaccine decreases Treg proportion and enhances anti-tumor responses in mice bearing melanoma].

Objective: To investigate the therapeutic effect of Toll-like receptor 7( TLR7) agonist imiquimod combined with dendritic cell( DC)-based tumor vaccine on melanoma in mice and the potential mechanism. Methods: Melanoma-bearing mouse models were established by subcutanous injection of B16-OVA cells into C57 BL /6 mice. DCs were isolated from mouse bone marrow and propagated in culture medium with recombinant mouse granulocyte-macrophage colony-stimulating factor( rm GM-CSF) and recombinant mouse interleukin-4( rm IL-4). DC vaccine( OVA-DC) was prepared by overnight incubation of DCs added with chicken ovalbumin. C57 BL /6 mice were separated into four groups which were treated with PBS,topical imiquimod application,OVA-DC intradermal injection and imiquimod plus OVA-DC,respectively. The tumor size was calculated by digital vernier caliper. Peripheral blood CD4~+FOXP3~+Tregs of the tumor-bearing mice was detected by flow cytometry. The cytotoxicity of splenic lymphocyte against B16-OVA was assessed in vitro by CCK-8 assay. Results: Compared with the other three groups,B16-OVA-bearing mice treated with imiquimod plus DC vaccine had the smallest tumor volume. The percentage of CD4~+FOXP3~+Tregs decreased significantly in the combined treated mice. The combined treatment enhanced significantly cytotoxicity of splenic lymphocytes against B16-OVA cells. Conclusion: Imiquimod combined with antigen-pulsed-DC vaccine could reduce CD4~+FOXP3~+Treg proportion and promote anti-tumor effect in mice with melanoma