Extracellular Vesicles from Carcinoma-Associated Fibroblasts Promote Epithelial-Mesenchymal Transition of Salivary Adenoid Cystic Carcinoma via Interleukin-6

Carcinoma-associated fibroblasts (CAF) play a pivotal role in cancer progression. Salivary adenoid cystic carcinoma (SACC) has a high tendency to invade and metastasize. Understanding how CAF interact with SACC cells is essential to develop new targeting therapies for SACC. Extracellular vesicles (EVs) play important roles in intercellular communication. However, the role of CAF-derived EVs in SACC invasion remains poorly understood. In this study, we show that CAF EVs promote the migration and invasion abilities of SACC cells. The expression of biomarkers of epithelial-mesenchymal transition (EMT) was higher in SACC cells treated with CAF EVs treated with CAF EVs than in the negative controls, and high levels of IL-6 were detected in CAF and their EVs. Knockdown of IL-6 in CAF decreased invasive abilities and EMT biomarker expression in SACC cells induced by CAF EVs. CAF EV-associated IL6 promoted SACC EMT by activating JAK2/STAT3 signaling pathway. These findings suggest that targeting CAF-derived EVs may be an effective strategy for inhibiting SACC invasion.

CALCB rs3829222 T/T Genotype and Low Expression of CALCB Are High-Risk Factors for Adenoid Cystic Carcinoma of Salivary Gland

Objectives. To investigate the relationship between polymorphisms of calcitonin-related peptide gene II (beta-calcitonin gene-related peptide (βCGRP), CALCB) and serum CGRP levels in salivary adenoid cystic carcinoma. Materials and Methods. Using the polymerase chain reaction (PCR) technique, the full-length amplification and genotype analysis of CALCB genes were performed in 39 patients with adenoid cystic carcinoma of salivary gland and 158 normal controls. The gene frequencies of major genotype of CALCB in adenoid cystic carcinoma of salivary gland and normal control group were analyzed. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate serum calcitonin gene-related peptide (CGRP) and its concentration of alpha and beta subtypes. Results. Univariate logistic regression analysis showed that the CALCB rs2839222 T/T genotype was closely related to the occurrence of salivary adenoid cystic carcinoma, with a correlation coefficient of 3.89. Conclusions. The serum CGRP concentration in the salivary adenoid cystic carcinoma group was 1.56 times that of the normal control group. The αCGRP subtype was significant, which was 3.02 times that of the normal control. The polymorphism of βCGRP gene is associated with genetic susceptibility to salivary adenoid cystic carcinoma, and serum CGRP and βCGRP can be used as novel markers of salivary adenoid cystic carcinoma.

Inhibition of DEC2 is necessary for exiting cell dormancy in salivary adenoid cystic carcinoma

Background Patients were prone to have poor prognosis once dormant tumor cells being reactivated. However, the molecular mechanism of tumor cell dormancy remains poorly understood. This study aimed to investigate the function of DEC2 in the dormancy of salivary adenoid cystic carcinoma (SACC) in vitro and vivo. Methods The function of DEC2 in tumor dormancy of SACC was investigated in nude mice by establishing primary and lung metastasis model. Meanwhile, the interaction between hypoxia and SACC dormancy and the role of DEC2 were demonstrated through CoCl2 induced hypoxia–mimicking microenvironments. Furthermore, the expression of DEC2 was detected by immunohistochemical staining in primary SACC samples with and without recurrence. Results In the primary SACC, DEC2 overexpression inhibited cell proliferation, increased cell population arrested in G0/G1 phase, and participated in dormancy regulation, which limited tumor growth. Intriguingly, in the model of lung metastasis, the level of DEC2 was reduced significantly and resulted in dormancy exit and growth resumption of SACC cells. Then, we found that DEC2 may associate with hypoxia in contributing to tumor dormancy, which might provide a possible cue to explain the different roles of DEC2 in primary and metastasis lesions. And overexpression of DEC2 induced dormancy and promoted migration and invasion through activating EMT program. Finally, DEC2 positive expression was shown to be significantly correlated with recurrence and dormancy of SACC patients. Conclusions These findings provide a novel insight into the role of DEC2 gene in tumor dormancy and metastasis.