Contactin-1 (CNTN-1) Overexpression is Correlated with Advanced Clinical Stage and Lymph Node Metastasis in Oesophageal Squamous Cell Carcinomas

Abstract

Objective: Oesophageal squamous cell carcinoma is one of the deadliest malignancies worldwide. Contactin-1, a neural adhesion molecule, is implicated in tumour invasion and metastasis. The purpose of this study was to investigate the expression of CNTN-1 in normal and cancerous oesophageal tissue, and the potential relevance to clinicopathological features. Methods: Thirty normal oesophageal tissue samples and 82 primary oesophageal squamous cell carcinoma tissue samples were included in this study. The expression levels of CNTN-1, VEGF-C and HIF-1a messenger RNA were determined using reverse transcriptase -polymerase chain reaction and quantitative real-time polymerase chain reaction. The expression of the CNTN-1 protein was measured using immunohistochemistry. Results: The expression of CNTN-1 messenger RNA was significantly increased in the tumour tissue compared with the normal oesophageal tissue (P ¼ 0.001). The oesophageal squamous cell carcinoma tissue consistently showed higher CNTN-1 protein levels. The CNTN-1 expression correlated with the oesophageal squamous cell carcinoma stage (P ¼ 0.006), lymph node metastasis (P ¼ 0.018) and lymphatic invasion (P ¼ 0.035). The messenger RNA level of CNTN-1 correlated significantly with those of VEGF-C and HIF-1a. Conclusions: The expression of CNTN-1 is upregulated in the oesophageal squamous cell carcinoma tissue and related to stage, lymph node metastasis and lymphatic invasion. Thus, CNTN-1 may be involved in the progression and pathogenesis of oesophageal squamous cell carcinoma.

Increased sensitivity of human lung adenocarcinoma cells to cisplatin associated with downregulated contactin-1

“…In oesophageal cancer, cell proliferation and migration induced by VEGF-C are reversed by CNTN-1 silencing, which suggested that VEGF-C promotes the development of oesophageal cancer by regulating CNTN-1 expression [20]. The comparison of CNTN-1 expression between normal oesophageal tissue samples and primary oesophageal squamous cell carcinoma tissue samples using IHC demonstrated that CNTN-1 was correlated with stage, lymph node metastasis, and lymphatic invasion [21]. Additionally, CNTN-1 expression was found to be significantly associated with the overall survival and the disease-free survival of patients with oral squamous cell carcinoma (OSCC) [22].…”

“…Subsequent study revealed that CNTN-1 was associated with invasive ability and to inversely correlate with the prognosis of lung adenocarcinoma patients, and it was proposed to function in the invasion and metastasis of lung adenocarcinoma cells via RhoA-mediated mechanisms [19]. Studies in oesophageal squamous cell carcinoma [20,21], oral squamous cell carcinoma [22], and gastric cancer [23] further confirmed that CNTN-1 plays a critical role in the development, progression, and pathogenesis of these tumours.…”

CNTN-1 Enhances Chemoresistance in Human Lung Adenocarcinoma Through Induction of Epithelial-Mesenchymal Transition by Targeting the PI3K/Akt Pathway

“…Recently, CNTN-1 was demonstrated to be able to promote invasion, metastasis and proliferation in prostate cancer [43], thyroid cancer [44], gastric cancer [35, 45-46], lung cancer [32-33], esophageal squamous cancer [30, 47], and oral squamous cancer [31]. Additionally, in our previous studies, CNTN-1 was found to enhance the metastasis, invasion, and chemoresistance of lung cancer cells [36].…”

“…In recent years, the abnormal expression of CNTN-1 was reported to be closely correlated with carcinogenesis and tumor progression [11, 30-34]. Furthermore, the elevated expression of CNTN-1 was demonstrated to facilitate metastasis of MKN45 gastric cancer cells via activation of the EMT process [35].…”

Neural Cell Adhesion Protein CNTN1 Promotes the Metastatic Progression of Prostate Cancer

“…Interestingly, in addition to L1CAM, increased expression of contactin 1 (CNTN1 and F3/contactin) was detected in lung carcinoma. CNTN1 promoted lung cancer metastasis (11,12) and its expression associated with poor prognosis for patients with lung carcinoma, esophageal, and oral squamous cell carcinomas (11,13,14). Nevertheless, to the best of our knowledge, the role of CNTN1 in prostate cancer progression and metastasis is unknown.…”