Wael Abdo Hassan1, Ryoji Yoshida2, Shinji Kudoh3, Koki Hasegawa3, Kanako Niimori-Kita3, Takaaki Ito4. 1. Department of Pathology and Experimental Medicine, Kumamoto University, Graduate School of Medical Sciences, Japan; Department of Pathology, Faculty of Medicine, Suez Canal University, Egypt. 2. Department of Oral and Maxillofacial Surgery, Kumamoto University, Graduate School of Medical Sciences, Japan. 3. Department of Pathology and Experimental Medicine, Kumamoto University, Graduate School of Medical Sciences, Japan. 4. Department of Pathology and Experimental Medicine, Kumamoto University, Graduate School of Medical Sciences, Japan. Electronic address: takaito@kumamoto-u.ac.jp.
Abstract
INTRODUCTION: Notch signaling plays a key role in a wide variety of human neoplasms, and it can be either oncogenic or anti-proliferative. Moreover, Notch function in regulating cancer is unpredictable, and its outcome is strictly context-dependent. AIM: To study the role of Notch1 signaling in human small cell lung carcinoma (SCLC) and its effect on cell invasion and metastasis. MATERIALS AND METHODS: We used small interfering RNA (siRNA) technology, to down-regulate the expression of Notch1 in H69AR and SBC3 SCLC cells. On the other hand, we up-regulated Notch1 in H69 and H1688 SCLC cells through transfection with venus Notch1 intracellular domain (v.NICD) plasmid. In addition, H69 cells with v.NICD were xenotransplanted into immune-compromised Rag2(-/-) Jak3(-/-) mice, for analysis of ex vivo tumor epithelial mesenchymal transition (EMT) phenotype and for detection of metastatic cancer cells in the lung tissues. Moreover, we examined the metastatic ability for H69AR and SBC3 cells transfected with siRNA against Notch1, compared to their subsequent controls, by use of tail vein xenograft mouse models. RESULTS: Notch1 controls cell adhesion and EMT. Overexpression of Notch1 in SCLC switched off EMT, cell motility and cell metastatic potential. CONCLUSION: Our results demonstrate that activation of Notch1 signaling pathway may represent a new strategy for treating human SCLC.
INTRODUCTION:Notch signaling plays a key role in a wide variety of humanneoplasms, and it can be either oncogenic or anti-proliferative. Moreover, Notch function in regulating cancer is unpredictable, and its outcome is strictly context-dependent. AIM: To study the role of Notch1 signaling in humansmall cell lung carcinoma (SCLC) and its effect on cell invasion and metastasis. MATERIALS AND METHODS: We used small interfering RNA (siRNA) technology, to down-regulate the expression of Notch1 in H69AR and SBC3 SCLC cells. On the other hand, we up-regulated Notch1 in H69 and H1688 SCLC cells through transfection with venus Notch1 intracellular domain (v.NICD) plasmid. In addition, H69 cells with v.NICD were xenotransplanted into immune-compromised Rag2(-/-) Jak3(-/-) mice, for analysis of ex vivo tumor epithelial mesenchymal transition (EMT) phenotype and for detection of metastatic cancer cells in the lung tissues. Moreover, we examined the metastatic ability for H69AR and SBC3 cells transfected with siRNA against Notch1, compared to their subsequent controls, by use of tail vein xenograft mouse models. RESULTS:Notch1 controls cell adhesion and EMT. Overexpression of Notch1 in SCLC switched off EMT, cell motility and cell metastatic potential. CONCLUSION: Our results demonstrate that activation of Notch1 signaling pathway may represent a new strategy for treating humanSCLC.