Notch1 controls cell invasion and metastasis in small cell lung carcinoma cell lines

Wael Abdo Hassan; Ryoji Yoshida; Shinji Kudoh; Koki Hasegawa; Kanako Niimori-Kita; Takaaki Ito

doi:10.1016/j.lungcan.2014.10.007

Notch1 controls cell invasion and metastasis in small cell lung carcinoma cell lines

Lung Cancer. 2014 Dec;86(3):304-10. doi: 10.1016/j.lungcan.2014.10.007. Epub 2014 Oct 22.

Authors

Wael Abdo Hassan¹, Ryoji Yoshida², Shinji Kudoh³, Koki Hasegawa³, Kanako Niimori-Kita³, Takaaki Ito⁴

Affiliations

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.

PMID: 25456735
DOI: 10.1016/j.lungcan.2014.10.007

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.

Keywords: Cell metastatic potential; Cell motility; Epithelial mesenchymal transition (EMT); Notch1 signaling; Small cell lung carcinoma (SCLC); Tail vein xenograft mouse model.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line, Tumor
Epithelial-Mesenchymal Transition
Gene Expression Regulation, Neoplastic
Humans
Mice
Neoplasm Invasiveness / genetics*
Neoplasm Invasiveness / pathology
Neoplasm Metastasis
Receptor, Notch1 / biosynthesis
Receptor, Notch1 / genetics*
Signal Transduction
Small Cell Lung Carcinoma / genetics*
Small Cell Lung Carcinoma / pathology
Xenograft Model Antitumor Assays

Substances

NOTCH1 protein, human
Receptor, Notch1