Emerging evidence indicates that mesenchymal stem cells (MSCs) serve an indispensable role in the tumor microenvironment. However, whether MSCs participate in the development of oral carcinogenesis remains unclear. The present study isolated MSCs from clinical tissues and investigated the differences of MSCs derived from normal oral mucosa (N-MSC), oral leukoplakia with dysplasia (LK-MSC) and oral carcinoma (Ca-MSC). The results revealed that the LK-MSCs exhibited reduced proliferation and migration, compared with the N-MSCs and Ca-MSCs. Furthermore, it was demonstrated that the exosomes secreted by LK-MSCs have significant roles in promoting proliferation, migration and invasion in vitro , which was similar to the Ca-MSC-derived exosomes. The promoting effect was also demonstrated in a 3D coculture model. When the secretion of exosomes was blocked, the promoting effect of LK-MSCs was reversed. Based on a microarray analysis of MSC-derived exosomes, microRNA-8485 (miR-8485) was identified to be ectopically expressed. The exosomal miR-8485 was capable of promoting the proliferation, migration and invasion of tumor cells. Therefore, the present study highlights the significance of MSC-derived exosomes and exosomal miR-8485 in premalignant lesions and carcinogenesis. Intervention with the secretion of MSC-derived-exosomes may be an innovative strategy to retard the carcinogenesis.

Background: Photodynamic therapy (PDT) has demonstrated promising results in the treatment of oral leukoplakia. This study evaluated the clinical efficacy and side effects of PDT in the treatment of Chinese patients with oral leukoplakia.Methods: Twenty-nine patients with oral leukoplakia were enrolled in this study, including patients with both homogenous and non-homogenous lesions and various dysplastic tissues. All patients received PDT using a 632 nm laser at 500 mW/cm2 power density at a dosage of 90–180 J/cm2 and with aminolevulinic acid (ALA) used as a photosensitizer. A fixing and restricting complex as well as high laser power density for PDT in oral cavity was applied.Results: An overall response rate of 86.2% was achieved in this study, including 55.2% complete remission and 31.0% partial remission. The only adverse events observed in subjects were transient local ulcer and pain. It is observed the PDT utilizing ALA showed strong effectiveness in patients with moderate to severe dysplasia, as less treatment time per cm2 of lesion is required.Conclusion: Topic ALA-PDT is effective to treat oral leukoplakia, especially for that with the presence of dysplasia. A fixing and restricting complex as well as high laser power density for PDT in oral cavity should be considered as an optimal choice.

The interplay between tumor cells and mesenchymal stem cells (MSCs) within tumor microenvironment plays a significant role in tumor development, and thus might be exploited for therapeutic intervention. In this study, we isolated MSCs from normal gingival tissue (GMSCs), and detected the effect of GMSCs on oral cancer cells via direct co-culture and indirect co-culture systems. The cell proliferation assay of direct co-culture showed that GMSCs could inhibit the growth of oral cancer cells. Conditioned medium derived from GMSCs (GMSCs-CM) also exerted an anticancer effect, which indicates that soluble factors in GMSCs-CM played a dominant role in GMSCs-induced cancer cell growth inhibition. To investigate the mechanism, we performed apoptosis assay by flow cytometry, and confirmed that cancer cell apoptosis induced by GMSCs could be a reason for the effect of GMSCs on the growth of oral cancer cells. Western blotting also confirmed that GMSCs could upregulate expression of pro-apoptotic genes including p-JNK, cleaved PARP, cleaved caspase-3, Bax expression and downregulate proliferation- and anti-apoptosis-related gene expression such as p-ERK1/2, Bcl-2, CDK4, cyclin D1, PCNA and survivin. Importantly, the inhibitory effect of GMSCs on cancer cells can partially be restored by blockade of JNK pathway. Moreover, animal studies showed that GMSCs exerted an anticancer effect after oral cancer cells and GMSCs were co-injected with oral cancer cells. Taken together, our data suggest that GMSCs can suppress oral cancer cell growth in vitro and in vivo via altering the surrounding microenvironment of oral cancer cells, which indicates that GMSCs have a potential use in the management of oral dysplasia and oral cancer in future.

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