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Recent studies have demonstrated that mesenchymal stem cells (MSC) exhibit a tropism to tumors and form the tumor stroma. In addition, we found that MSC can secrete different types of factors. However, the involvement of MSC-derived factors in human tongue squamous cell carcinoma (TSCC) growth has not been clearly addressed. The CCN family includes multifunctional signaling molecules that affect the initiation and development events of various tumors. In our study, we report that CCN2/connective tissue growth factor (CTGF) was the most highly induced among the CCN family members in MSC that were co-cultured with TSCC cells. To evaluate the relationship between CCN2 and TSCC growth, we downregulated MSC-derived CCN2 expression with shRNA targeting CCN2 and found that MSC-secreted CCN2 promotes TSCC cell proliferation, migration and invasion. We also confirmed that MSC-derived CCN2 partially accelerated tumor growth in vitro. Taken together, these results suggest that MSC-derived CCN2 contributes to the promotion of proliferation, migration and invasion of TSCC cells and may be a possible therapy target in the future., (© 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Platelet-derived growth factor D (PDGF-D) signaling plays significant roles during the development and progression of human malignancies via interacting with the receptor of PDGF-D (PDGFR). Meanwhile, the majority of human tumor metastasis is closely associated with epithelial-mesenchymal transition (EMT). However, the underlying mechanism between PDGF-D/PDGFR signaling and EMT which involved in tumor metastasis remain dismal. This study aimed to investigate the role of PDGF-D signaling during EMT process of tongue squamous cell carcinoma (TSCC). In our study, the expression of PDGF-D and PDGFR were examined in primary TSCC samples and the expression of PDGF-D was also determined in TSCC cell lines. In addition, the correlation between PDGF-D expression and TSCC aggressive histopathological features was analyzed. Our results implied that upregulation of PDGFRβ in UM1 cells induced with exogenous PDGF-D can remarkably promote tumor cells invasiveness; conversely, when using small interfering RNA (siRNA), the invasiveness can be severely prohibited. Furthermore, PDGF-D downstream signal molecules p38, AKT, ERK and EMT biomarkers (E-cadherin, N-cadherin, Vimentin and snail) were measured using Western blot. Our results showed that PDGF-D can induce p38, AKT and ERK phosphorylation; downregulate epithelial markers and upregulate mesenchymal markers. On the contrary, PDGFRβ siRNA significantly prohibited p38, AKT and ERK phosphorylation; inhibited EMT process. Function analysis revealed that PDGFRβ siRNA obviously interfered with UM1 cell migration and invasion, according to transwell and wound healing assay. In conclusion, this study suggested that EMT process can be triggered by the PDGF-D/PDGFRβ axis in TSCC, and then involved in the tumor cell invasion via activation of p38/AKT/ERK/EMT pathway., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Metastasis to long distance organs is the main reason leading to morality of tongue squamous cell carcinoma (TSCC); however, the molecular mechanisms are still unknown. High mobility group AT-hook 2 (HMGA2) is highly expressed in multiple metastatic carcinomas, in which it contributes to cancer progression, metastasis and poor prognosis by upregulating Snail expression and inducing epithelial mesenchymal transition (EMT). This study focuses on investigating the role and mechanism of regulation of HMGA2 in the metastasis of TSCC., Methods: HMGA2 mRNA and protein expression were examined in TSCC specimens by quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry (IHC). Western blotting, IHC and immunofluorescence were also used to measure the expression and localization of EMT marker E-Cadherin and Vimentin both in TSCC cells and tissues. Knockdown assay was performed in vitro in TSCC cell lines using small interfering RNAs and the functional assay was carried out to determine the role of HMGA2 in TSCC cell migration and invasion., Results: TSCC mRNA and protein expression were significantly up-regulated in tumor tissues when compared to adjacent non-tumor tissues, and the overexpression of HMGA2 was closely correlated with lymph nodes metastasis. Clinicopathological analysis indicated that HMGA2 expression was associated with clinical stage (P = 0.001), lymph node metastasis (P = 0.000), histological differentiation (P = 0.002) and survival (P = 0.000). Silencing the HMGA2 expression in Cal27 and UM1 resulted in the inhibition of cell migration and invasion, meanwhile down-regulation of HMGA2 impaired the phenotype of EMT in TSCC cell lines and tissues. The Multivariate survival analysis indicates that HMGA2 can be an independent prognosis biomarker in TSCC., Conclusion: Our findings demonstrate that HMGA2 promotes TSCC invasion and metastasis; additionally, HMGA2 is an independent prognostic factor which implied that HMGA2 can be a biomarker both for prognosis and therapeutic target of TSCC.

Objective: To explore the effect of the patients' articulator function after reconstruction of hemi-tongue defect with forearm flap (FAP) or prime close (PC)., Methods: 36 patients who underwent hemiglossectomy were investigated after radical surgery for TSCC. 20 cases were reconstructed with FAP flaps and 16 with primary closure. The patients' articulator functions were evaluated by articulation tests. VS-9700 was used to analyze the speech character when they pronounce /ji/., Results: 1) The speech articulation of patients who underwent hemi-tongue reconstruction with FAF was better than that of patients with PC, and there was significant difference between them (P < 0.05). 2) The first formant (F1) of /i/ of the PC group was lower than that of the control group (P < 0.05). But the second formant (F2) of the PC group was higher than that of the control group (P < 0.05). The first formant (F1) of /i/ of the FAF group was lower than that of the control group (P < 0.05), but there were no significant differences between FAF group and control group in F2 of /i/ (P > 0.05)., Conclusions: Articulator function can be well achieved by forearm flaps reconstruction to hemi-tongue defect patients.

Objective: To explore the clinical value and safety of using rib-major pectoralis myocutaneous flap carrying costal parietal pleura in combined repair of large soft and hard tissue defect caused by radical surgery of advanced tongue cancer., Methods: Six patients with advanced tongue carcinoma involving the floor of mouth and mandible were performed combined radical neck dissection with glossectomy and mandibulectomy, which caused large soft and hard tissue defect. Six rib-major pectoralis myocutaneous flaps carrying costal parietal pleura were transferred for immediate repair of the large defects. The rib flaps were applied for the repair of mandible, and the major pectoralis myocutaneous flaps were applied for the reconstruction of tongue and floor of mouth., Results: Six patients recovered well after operation. Six rib-major pectoralis myocutaneous flaps carrying costal parietal pleura survived well; the wounds of surgical incision of the oral cavity, neck, and chest healed up. The reconstructed tongue and the lower face appearance were satisfactory, the occlusion relationships were normal; the speaking as well as swallowing functions recovered., Conclusions: It's safe and reliable to use rib-major pectoralis myocutaneous flap carrying costal parietal pleura to repair large soft and hard tissue defect in oral and maxillofacial region. Opening pleural cavity and harvest costal parietal pleura would not influence patients' thoracic movement and breath function and would not cause other complications. It's simple and safe for harvesting the composite flap. Carrying costal parietal pleura assures the sufficient blood supply of rib in the composite flap.