Tumor- and Osteoblast-Derived Periostin in Prostate Cancer bone Metastases

Exploring the biological function of periostin (POSTN) in prostate cancer (PCa) bone metastasis is of importance. It was observed that the expression of POSTN was high in PCa, especially highest in PCa metastasized to bone. In this study, we found that inhibiting POSTN in PCa cells could significantly alleviate PCa bone metastasis in vivo, suggesting POSTN is a promising therapeutic target. Since, due to the secreted expression of POSTN in osteoblasts and PCa, we hypothesized the positive feedback loop between osteoblasts and PCa mediated by POSTN in PCa bone metastasis. The in vitro experiments demonstrated that osteoblast-derived POSTN promoted PCa cell proliferation and invasion and PCa cell-derived POSTN promotes proliferation of osteoblasts. Furthermore, we found that POSTN regulated PCa and osteoblast function through integrin receptors. Finally, 18F-Alfatide II was used as the molecule probe of integrin αvβ3 in PET-CT, revealing high intake in metastatic lesions. Our findings together indicate that targeting POSTN in PCa cells as well as in the osteoblastic may be an effective treatment for PCa bone metastasis.

High-Level Extracellular Expression of a New β-N-Acetylglucosaminidase in Escherichia coli for Producing GlcNAc

N-acetyl-β-D glucosamine (GlcNAc) is wildly used in cosmetics, nutraceuticals and pharmaceuticals. The traditional chemical process for GlcNAc production from chitin causes serious acidic pollution. Therefore, the enzymatic hydrolysis becomes a great promising and alternative strategy to produce GlcNAc. β-N-acetylglucosaminidase (NAGase) can hydrolyze chitin to produce GlcNAc. Here, a GH3 family NAGase encoding gene BlNagZ from Bacillus licheniformis was expressed extracellularly in Escherichia coli guided by signal peptide PelB. The recombinant BlNagZ presented the best activity at 60°C and pH 5.5 with a high specific activity of 13.05 U/mg. The BlNagZ activity in the fermentation supernatant can reach 13.62 U/mL after optimizing the culture conditions, which is 4.25 times higher than optimization before. Finally, combining BlNagZ with chitinase ChiA we identified before, chitin conversion efficiency to GlcNAc can reach 89.2% within 3.5 h. In all, this study provided not only a high active NAGase, and a secreted expression strategy to reduce the cost of production, which is conducive to the industrial application.

Combining 1,4-dihydroxy quininib with Bevacizumab/FOLFOX alters angiogenic and inflammatory secretions in ex vivo colorectal tumors

Background Colorectal cancer (CRC) is the second most common cause of cancer-related mortality worldwide with one in every five patients diagnosed with metastatic CRC (mCRC). In mCRC cases, the 5-year survival rate remains at approximately 14%, reflecting the lack of effectiveness of currently available treatments such as the anti-VEGF targeting antibody Bevacizumab combined with the chemotherapy folinic acid, fluorouracil and oxaliplatin (FOLFOX). Approximately 60% of patients do not respond to this combined treatment. Furthermore, Bevacizumab inhibits dendritic cell (DC) maturation in poor responders, a key process for tumor eradication. Method Following drug treatment, secreted expression levels of angiogenic and inflammatory markers in tumor conditioned media generated from human ex vivo colorectal tumors were measured by ELISA. Dendritic cell phenotypic and maturation markers were assessed by flow cytometry. Results Our novel compound, 1,4-dihydroxy quininib, acts in an alternative pathway compared to the approved therapy Bevacizumab. 1,4-dihydroxy quininib alone, and in combination with Bevacizumab or FOLFOX significantly reduced TIE-2 expression which is involved in the promotion of tumor vascularization. Combination treatment with 1,4-dihydroxy quininib significantly increased the expression level of DC phenotypic and maturation markers. Conclusion Our results indicate the anti-angiogenic small molecule 1,4-dihydroxy quininib could be an alternative novel treatment in combination therapy for CRC patients.