Human cells release nano-sized vesicles called exosomes, containing mRNA, miRNA and specific proteins. Exosomes from one cell can be taken up by another cell, which is a recently discovered cell-to-cell communication mechanism. Also, exosomes can be taken up by different types of cancer cells, but the potential functional effects of mast cell exosomes on tumor cells remain unknown. Exosomes were isolated from the human mast cell line, HMC-1, and uptake of PKH67-labelled exosomes by the lung epithelial cell line, A549, was examined using flow cytometry and fluorescence microscopy. The RNA cargo of the exosomes was analyzed with a Bioanalyzer and absence or presence of the c-KIT mRNA was determined by RT-PCR. The cell proliferation was determined in a BrdU incorporation assay, and proteins in the KIT-SCF signaling pathway were detected by Western blot. Our result demonstrates that exosomes from mast cells can be taken up by lung cancer cells. Furthermore, HMC-1 exosomes contain and transfer KIT protein, but not the c-KIT mRNA to A549 cells and subsequently activate KIT-SCF signal transduction, which increase cyclin D1 expression and accelerate the proliferation in the human lung adenocarcinoma cells. Our results indicate that exosomes can transfer KIT as a protein to tumor cells, which can affect recipient cell signaling events through receptor-ligand interactions.

Recent evidence has shown that C-X-C chemokine receptor type 4 (CXCR4) plays a crucial role in acute lung injury (ALI). Macrophages are key factors in the pathogenesis of ALI. The aim of this study was to investigate the role of CXCR4 in macrophages after lipopolysaccharide (LPS) stimulation and confirm that CXCR4 knockdown can inhibit inflammatory cytokines by suppressing mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathway activation. In this study, we found that CXCR4 expression in lung tissue of ALI was significantly increased using immunofluorescence. We also found that the expression of CXCR4 in macrophages sorted from bronchoalveolar lavage fluid (BALF) of ALI was obviously upregulated through RT-qPCR. After CXCR4 knockdown using siRNA, we found that the expression of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) was obviously down regulated in macrophages. Additionally, the phosphorylation of p38, Erk, and p65 was significantly decreased after CXCR4 knockdown through western blotting. Taken together, the present study suggests that CXCR4 knockdown may inhibit inflammatory cytokine expression in macrophages by suppressing MAPK and NF-κB signaling pathway activation. Therefore, CXCR4 knockdown may have potential clinical value in treating ALI.

HuR overexpression is related to poor survival in patients with colon cancer. HuR overexpression leads to stabilization of tumor-promoting mRNAs by binding to 3′UTR-resident AREs. Exosomes, nanosized lipid bilayer vesicles, mediate many steps in cancer progression. The potential role of exosomal HuR in colon cancer lung metastasis is unclear. HuR expression was assessed immunohistochemically in tumor tissue samples from 20 patients with metastatic or nonmetastatic colon cancer and colon cancer lung metastasis and benign lung disease samples from ten patients. Exosomes were isolated from HCT116 WT and HuR KO colon cancer cells, and uptake of PKH67- and PKH26-labeled exosomes by BEAS-2B cells was evaluated using fluorescence and confocal microscopy. C-Myc and p21protein and mRNA levels were measured by western blotting and RT-qPCR, respectively. In clinical patients, HuR overexpression was significantly enhanced in colon tissues of patients with lung metastasis. HuR expression was higher in lung tissue with metastasis of colonic origin than with benign lung disease. The effect of HuR-containing CRC exosomes compared to HuR-deficient exosomes on wound closure was observed as enhanced proliferation. BEAS-2B cell migration and invasion were enhanced after HuR-containing exosomes treatment. BEAS-2B cells showed similar uptake of PKH67 (HCT116 WT)- and PKH26 (HCT116 HuR KO)-labeled exosomes. Exosomal HuR stabilized c-Myc mRNA and downregulated p21 expression, leading to G1/S transition, in human bronchial epithelial cells. HuR overexpression is associated with lung metastasis in colon cancer patients. Exosomal HuR derived from colon cancer cells alter the biological effect on normal lung epithelial cells.

Objective: Solitary pulmonary nodules (SPNs) is a common radiographic finding and require further evaluation because of the possibility of lung cancer. This study aimed to determine the sensitivity and specificity of circulating tumour cells (CTCs) as a marker for the diagnosis of SPNs and the integration of CTCs, carcinoembryonic antigen (CEA) and imaging findings to improve the sensitivity and specificity of diagnosis in patients with SPNs suspected of being lung cancer. Method: For the serum biomarker assay, the concentration of CEA was measured by an automated electrochemiluminescence analyzer. CTCs were collected from 6 ml of blood by the SE i-FISH method, which detects the gene copy number in eight chromosomes and the tumour-associated antigen CK18. Results: With a threshold of 6 CTC units, the method showed a sensitivity of 67.1% and a specificity of 56.5% in the diagnosis of NSCLC, especially in the upper lobe, in which the diagnostic strength was the highest (P < 0.01). CTCs, CEA and nodule type had the highest diagnostic efficacy (area under the curve, 0.827; 95% confidence interval, 0.752–0.901) in patients with SPNs being suspected lung cancer. Combining CTCs (cut-off value 12 units) with CEA (1.78 ng/ml), the method showed a sensitivity of 77.8% and a specificity of 90% in the diagnosis of NSCLC, especially in the upper lobe, subsolid nodules and nodules ≥8 mm. Conclusions: Our results demonstrated that CTCs are feasible diagnostic biomarkers in patients with SPNs, especially in the upper lobe. Furthermore, CTCs combined with CEA showed higher diagnostic efficacy in the upper lobe, subsolid nodules and nodules ≥8 mm.

Objective: The aim of this study was to investigate whether echo intensity of the rectus femoris when measured using ultrasound can distinguish muscles affected by COPD compared with healthy non-COPD affected muscles and whether the severity of ultrasonic abnormalities was associated with health-related quality of life (HRQoL). Methods: Echo intensity, areas of the rectus femoris, and the thickness of quadriceps muscles were measured using ultrasound in 50 COPD outpatients and 21 age-matched non-COPD controls. The results of the 8-Item Short-Form Health Survey and the functional assessment of chronic illness therapy fatigue scales were used to evaluate HRQoL. Results: There was a significantly higher echo intensity of the rectus femoris in all stages of COPD patients than in age-matched non-COPD subjects; the quadriceps muscle thickness and cross-sectional area of the rectus femoris significantly decreased in COPD GOLD III–IV only. Furthermore, in our stable COPD patients, echo intensity of the rectus femoris was associated with HRQoL independently.
Conclusion: Quantitative ultrasound distinguishes healthy muscles from those affected by COPD grade I–IV, and quality and quantity of muscles are associated with HRQoL and forced expiratory volume in 1 second. Ultrasonic echo intensity of the rectus femoris may be a useful instrument for assessing disease severity and monitoring the changes of skeletal muscle resulting from disease progression or clinical intervention in patients with COPD.

Background: Coagulation disorders are a significant cause of lung cancer mortality. Although mast cells are known to play a role in coagulation abnormalities, their specific role in this process has not yet been elucidated. Method: We detected mast cells in the tumor microenvironment using single-cell sequencing data and examined their correlation with thrombosis-related genes, neutrophil-related genes, neutrophil extracellular trap-related signature genes, and immune infiltration levels in lung cancer patients through bioinformatics analysis. Bone marrow mast cell uptake of exosomes isolated from the lung adenocarcinoma cell line A549, which were labeled using PKH67, was observed using confocal microscopy. Mast cell degranulation was detected by measuring the β-hexosaminidase release rate. Additionally, cytokine array analysis was performed to identify altered mediators released by bone marrow mast cells after uptake of the exosomes. Results: In our study, we found a close correlation between the proportion of mast cells in lung cancer patients and the expression levels of thrombosis-related genes and neutrophil extracellular trap signature genes, both of which play a key role in thrombophilic disorder. Moreover, we discovered that lung cancer cell-derived exosomes can be taken up by mast cells, which in turn become activated to release procoagulant mediators. Conclusion: Our study shows that exosomes derived from lung cancer cells can activate mast cells to release procoagulants that may contribute to abnormal blood clotting in lung cancer patients.