Cancer-associated fibroblast-derived extracellular vesicles promote lymph node metastases in oral cavity squamous cell carcinoma by encapsulating ITGB1 and BMI1.

BACKGROUND: Extracellular vesicles (EVs) have been revealed to facilitate the development of oral squamous cavity cell carcinoma (OCSCC), while its supporting role in lymph node metastases is under continuous investigation. This study aimed to examine the function of cancer-associated fibroblasts (CAF)-derived EVs (CAF-EVs) during lymph node metastasis in OCSCC and the mechanisms. METHODS: CAF were isolated from OCSCC tissues of patients, and CAF-EVs were extracted and identified. EdU, colony formation, wound healing, and Transwell assays were performed. The OCSCC cells before and after CAF-EVs treatment were injected into mice to probe the effects of CAF-EVs on tumor growth and lymph node metastasis, respectively. The effect of CAF-EVs treatment on transcriptome changes in OCSCC cells was analyzed. Clinical data of patients with OCSCC were analyzed to determine the prognostic significance of the selected genes. Finally, loss-of-function assays were conducted to corroborate the involvement of polycomb complex protein BMI-1 (BMI1) and integrin beta1 (ITGB1). RESULTS: CAF-EVs promoted the malignant behavior of OCSCC cells and accelerated tumor growth and lymph node metastasis in mice. CAF-EVs significantly increased the expression of BMI1 and ITGB1, and the expression of BMI1 and ITGB1 was negatively correlated with the overall survival and relapse-free survival of OCSCC patients. Knockdown of BMI1 or ITGB1 in OCSCC cells abated the promoting effects of CAF-EVs in vitro and in vivo. CONCLUSION: CAF-EVs elicited the metastasis-promoting properties in OCSCC by elevating BMI1 and ITGB1, suggesting that BMI1 and ITGB1 could be potential biomarkers and therapeutic targets for OCSCC.

Potential Implications of the Lung Microbiota in Patients with Chronic Obstruction Pulmonary Disease and Non-Small Cell Lung Cancer.

Recently, chronic obstructive pulmonary disease (COPD) has been considered as a common risk factor of non-small cell lung cancer (NSCLC). However, very few studies have been conducted on the effects of COPD on the lung microbiota in patients with NSCLC. To identify the lung microbiota in patients with COPD and NSCLC (CN), the microbiome of the induced sputa of 90 patients was analyzed using 16S rDNA sequencing. The results showed no significant differences in the bacterial diversities of induced sputa among patients with COPD, NSCLC, and CN and no intrinsic differences among patients with different pathological types of lung cancer. After surgical operation, the diversities of the induced sputa in patients with CN significantly decreased. More remarkably, both the microbial community phenotypes and the components of the induced sputa in patients with CN obviously differed from those in patients with COPD or NSCLC. The relative abundances of Streptococcus, Veillonella, Moraxella, and Actinomyces significantly decreased, but those of Neisseria and Acinetobacter significantly increased in patients with CN compared with those in patients with COPD or NSCLC alone, resulting in increased Gram-negative microbiota and, therefore, in potential pathogenicity and stress tolerance, as well as in enhancement of microbial glycolipid metabolism, amino acid metabolism, and oxidative stress. Although COPD did not affect the number of pulmonary flora species in patients with NSCLC, these significant alterations in the microbial populations, phenotypes, and functions of induced sputa due to COPD would contribute to inflammation-derived cancer progression in patients with CN.