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Multidimensional Coculture System to Model Lung Squamous Carcinoma Progression
Published on: March 17, 2020
Expression of Draxin in Lung Carcinomas
Younosuke Sato1, Akira Matsuo1, Shinji Kudoh1
1Department of Pathology and Experimental Medicine, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan.
Abstract:
Guidance molecules, such as Netrin-1, and their receptors have important roles in controlling axon pathfinding, modulate biological activities of various cancer cells, and may be a useful target for cancer therapy. Dorsal repulsive axon guidance protein (Draxin) is a novel guidance molecule that binds not only common guidance molecule receptors with Netrin-1, but also directly binds the EGF domain of Netrin-1 through a 22-amino-acid peptide (22aa). By immunostaining, Draxin was positively expressed in small cell carcinoma, adenocarcinoma (ADC), and squamous cell carcinoma of the lung. In addition, western blot analysis revealed that Draxin was expressed in all histological types of lung cancer cell lines examined. Knockdown of Draxin in an ADC cell line H358 resulted in altered expression of molecules associated with proliferation and apoptosis. The Ki-67 labeling index of Draxin-knockdown ADC cells was increased compared to that of control ADC cells. In H358 cells, treatment of 22aa induced phosphorylation of histone H3, but did not change apoptosis-associated enzymes. These data suggest that Draxin might be involved in cell proliferation and apoptosis in lung adenocarcinoma cells.
Insights
Dorsal repulsive axon guidance protein (Draxin) is expressed in lung cancer cells and may influence cancer cell proliferation and apoptosis. Further research is needed to explore Draxin as a potential therapeutic target.
Area of Science:
- Neuroscience
- Molecular Biology
- Oncology
Background:
- Guidance molecules like Netrin-1 regulate axon pathfinding and cancer cell biology.
- Dorsal repulsive axon guidance protein (Draxin) is a novel guidance molecule with potential roles in cancer.
Purpose of the Study:
- To investigate the expression and function of Draxin in lung cancer.
- To explore Draxin's potential as a therapeutic target for lung adenocarcinoma.
Main Methods:
- Immunostaining and western blot analysis to detect Draxin expression in lung cancer tissues and cell lines.
- Draxin knockdown in H358 adenocarcinoma cells to assess effects on proliferation and apoptosis markers.
- Treatment of H358 cells with a Draxin-binding peptide (22aa) to evaluate molecular responses.
Main Results:
- Draxin is expressed in various lung cancer types, including small cell carcinoma, adenocarcinoma, and squamous cell carcinoma.
- Draxin knockdown in lung adenocarcinoma cells altered the expression of proliferation and apoptosis-associated molecules.
- Draxin knockdown led to an increased Ki-67 labeling index, indicating enhanced proliferation.
Conclusions:
- Draxin is implicated in the regulation of cell proliferation and apoptosis in lung adenocarcinoma.
- Draxin represents a potential therapeutic target for lung adenocarcinoma treatment.
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