Mitotic spindle apparatus abnormalities in chronic obstructive pulmonary disease cells: A potential pathway to lung cancer

Jose Thaiparambil, Lingyun Dong, Diana Jasso, Jian An Huang, Randa A. El-Zein

Research output: Contribution to journalArticle

Abstract

Chronic obstructive pulmonary disease (COPD) is a long-term lung disease characterized by irreversible lung damage resulting in airflow limitation, abnormal permanent airspace enlargement, and emphysema. Cigarette smoking is the major cause of COPD with 15% to 30% of smokers developing either disease. About 50% to 80% of patients with lung cancer have preexisting COPD and smokers who have COPD are at an increased risk for developing lung cancer. Therefore, COPD is considered an independent risk for lung cancer, even after adjusting for smoking. A crucial early event in carcinogenesis is the induction of the genomic instability through alterations in the mitotic spindle apparatus. To date, the underlying mechanism by which COPD contributes to lung cancer risk is unclear. We hypothesized that tobacco smoke carcinogens induce mitotic spindle apparatus abnormalities and alter expression of crucial genes leading to increased genomic instability and ultimately tumorigenesis. To test our hypothesis, we assessed the genotoxic effects of a potent tobacco-smoke carcinogen [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, (NNK)] on bronchial epithelial cells from patients with COPD and normal bronchial epithelial cells and identified genes associated with mitotic spindle defects and chromosome missegregation that also overlap with lung cancer. Our results indicate that exposure to NNK leads to a significantly altered spindle orientation, centrosome amplification, and chromosome misalignment in COPD cells as compared with normal epithelial cells. In addition, we identified several genes (such as AURKA, AURKB, and MAD2L2) that were upregulated and overlap with lung cancer suggesting a potential common pathway in the transition from COPD to lung cancer.

Original languageEnglish (US)
Pages (from-to)923-933
Number of pages11
JournalCancer Prevention Research
Volume13
Issue number11
DOIs
StatePublished - Nov 1 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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