Year-end Sale % OFF 
Abstract
Recent studies have shown that Notch signaling is involved in many types of cancers, including oral squamous cell carcinomas (OSCCs). However, the role of Notch signaling in the tumor microenvironment is not yet fully understood. In this study, we investigated the roles of NOTCH3 signaling in cancer associated fibroblasts (CAFs) in OSCCs. Immunohistochemical study of 93 human tongue OSCC cases indicated that about one third of OSCCs showed NOTCH3 expression in CAFs, and that this expression significantly correlated with tumor-size. In vitro study showed that OSCC cell lines, especially HO1-N-1 cells stimulated NOTCH3 expression in normal human dermal fibroblasts (NHDFs) through direct cell-to-cell contact. Immunohistochemical and morphometric analysis using human OSCC samples demonstrated that NOTCH3 expression in CAFs significantly correlated with micro-vessel density in cancer stroma. In vitro angiogenesis assays involving co-culture of NHDFs with HO1-N-1 and human umbilical endothelial cells (HUVECs), and NOTCH3 knockdown in NHDFs using siRNA, demonstrated that HO1-N-1 cells significantly promoted tube formation dependent on NOTCH3-expression in NHDFs. Moreover, NOTCH3 expression in CAFs was related to poor prognosis of the OSCC patients. This work provides a new insight into the role of Notch signaling in CAFs associated with tumor angiogenesis and the possibility of NOTCH3-targeted molecular therapy in OSCCs.
Highlights
Head and neck cancer derives from the upper aerodigestive tract including the nasal cavity, paranasal sinuses, oral cavity, pharynx and larynx
The primary site into the blood stream and to establish distant metastasis in a secondary organ. This complex process is regulated by various angiogenic factors produced by the tumor microenvironment including by tumor cells, fibroblasts and macrophages
They discovered that NOTCH3 is a candidate angiogenic gene, whose expression was substantially increased in fibroblasts when cocultured with human umbilical vein endothelial cells (HUVECs) [24]
Summary
Head and neck cancer derives from the upper aerodigestive tract including the nasal cavity, paranasal sinuses, oral cavity, pharynx and larynx. The predominant malignancy in head and neck cancer is squamous cell carcinoma (SCC). Oral SCC (OSCC) is the most common type of head and neck cancer. According to the recent GLOBOCAN estimates, approximately 300,000 new lip/oral cavity cancer patients were diagnosed in 2012 worldwide [1]. The 5-year survival rate of OSCC patients still ranges from 40 to 60% [2, 3]. Investigation regarding the molecular mechanism that regulates malignant behaviors of OSCC will be needed for development of therapeutic approaches and improvement of the poor prognosis
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
