Abstract
Because oral squamous cell carcinomas (OSCCs) have a high potential for locoregional invasion and nodal metastasis, early detection and treatment are essential. A LAP2, emerin, MAN1 (LEM) domain containing 1 (LEMD1) is associated with local progression, clinical stage, nodal metastasis, poor prognosis, angiogenesis, and lymphangiogenesis in OSCC. Although LEMD is a cancer-testis antigen, the cancer-related signals related to LEMD1 remain unknown. In this study, we used a microarray analysis of OSCC cells to identify sushi repeat containing protein X-linked 2 (SRPX2) as a LEMD1-related downstream signal. LEMD1 expression was correlated with lymph node metastasis of OSCC according to the immunohistochemistry analysis. Furthermore, patients expressing SRPX2 had a significantly worse prognosis than those without SRPX2 expression. The concentration of SRPX2 in OSCC was positively correlated with the concentrations of LEMD1, urokinase plasminogen activator receptor (uPAR), and hepatocyte growth factor (HGF). In OSCC cells, SRPX2 secretion levels were elevated by interactions with uPAR and HGF. We also found that SRPX2 promotes endothelial cell proliferation and adhesion between endothelial cells and OSCC cells. These results suggest that SRPX2 might be a useful tumor marker for OSCC.
Highlights
Oral squamous cell carcinoma (OSCC) is an aggressive cancer with a strong invasiveness and metastatic potential
We focused on sushi repeat containing protein X-linked 2 (SRPX2) because it is one of the genes whose expression levels were greatly reduced in LEM domain containing 1 (LEMD1)-downregulated OSCC cells
We previously reported that LEMD1 is closely involved in tumor progression, nodal metastasis, and worse OSCC outcomes by acquiring invasiveness and angiogenic and lymphangiogenic potential [10]
Summary
Oral squamous cell carcinoma (OSCC) is an aggressive cancer with a strong invasiveness and metastatic potential. Approximately 354,864 new OSCC cases and 177,384 deaths were estimated to have occurred in 2018, representing 2% of all cancer cases and 1.9% of all cancer deaths [1]. In the United States, approximately 53,000 new patients are diagnosed with OSCC annually, and 10,860 individuals die of this disease each year [2]. OSCC is highly prevalent in India, Sri Lanka, and Papua New Guinea, and it is the leading cause of cancer death among men in India and Sri Lanka [1]. Despite advances in diagnostics and therapeutics for OSCC, the five-year survival rates over the last three decades have not improved significantly and have remained lower than 50% [3,4]. The molecular biological mechanism of OSCC must be elucidated to improve prognosis through early detection and effective treatment
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