Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel

Effect of cyclical intermittent hypoxia on Ad5CMVCre induced solitary lung cancer progression and spontaneous metastases in the KrasG12D+; p53fl/fl; myristolated p110fl/fl ROSA-gfp mouse.

Publication ,  Journal Article
Guo, X; Liu, Y; Kim, JL; Kim, EY; Kim, EQ; Jansen, A; Li, K; Chan, M; Keenan, BT; Conejo-Garcia, J; Lim, DC
Published in: PLoS One
2019

BACKGROUND: Epidemiological data suggests that obstructive sleep apnea (OSA) is associated with increased cancer incidence and mortality. We investigate the effects of cyclical intermittent hypoxia (CIH), akin to the underlying pathophysiology of OSA, on lung cancer progression and metastatic profile in a mouse model. METHODS: Intrathoracic injection of Ad5CMVCre virus into a genetically engineered mouse (GEM) KrasG12D+/-; p53fl/fl; myristolated-p110αfl/fl-ROSA-gfp was utilized to induce a solitary lung cancer. Male mice were then exposed to either CIH or Sham for 40-41 days until harvest. To monitor malignant progression, serial micro CT scans with respiratory gating (no contrast) was performed. To detect spontaneous metastases in distant organs, H&E and immunohistochemistry were performed. RESULTS: Eighty-eight percent of injected Ad5CMVCre virus was recovered from left lung tissue, indicating reliable and accurate injections. Serial micro CT demonstrated that CIH increases primary lung tumor volume progression compared to Sham on days 33 (p = 0.004) and 40 (p<0.001) post-injection. In addition, CIH increases variability in tumor volume on day 19 (p<0.0001), day 26 (p<0.0001), day 33 (p = 0.025) and day 40 (p = 0.004). Finally, metastases are frequently detected in heart, mediastinal lymph nodes, and right lung using H&E and immunohistochemistry. CONCLUSIONS: Using a GEM mouse model of metastatic lung cancer, we report that male mice with solitary lung cancer have accelerated malignant progression and increased variability in tumor growth when exposed to cyclical intermittent hypoxia. Our results indicate that cyclical intermittent hypoxia is a pathogenic factor in non-small cell lung cancer that promotes the more rapid growth of developing tumors.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2019

Volume

14

Issue

2

Start / End Page

e0212930

Location

United States

Related Subject Headings

  • X-Ray Microtomography
  • Tumor Suppressor Protein p53
  • Solitary Pulmonary Nodule
  • Ribs
  • Proto-Oncogene Proteins p21(ras)
  • Neoplasm Metastasis
  • Myocardium
  • Mice, Transgenic
  • Mice
  • Mediastinum
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Guo, X., Liu, Y., Kim, J. L., Kim, E. Y., Kim, E. Q., Jansen, A., … Lim, D. C. (2019). Effect of cyclical intermittent hypoxia on Ad5CMVCre induced solitary lung cancer progression and spontaneous metastases in the KrasG12D+; p53fl/fl; myristolated p110fl/fl ROSA-gfp mouse. PLoS One, 14(2), e0212930. https://doi.org/10.1371/journal.pone.0212930
Guo, Xiaofeng, Yan Liu, Jessica L. Kim, Emily Y. Kim, Edison Q. Kim, Alexandria Jansen, Katherine Li, et al. “Effect of cyclical intermittent hypoxia on Ad5CMVCre induced solitary lung cancer progression and spontaneous metastases in the KrasG12D+; p53fl/fl; myristolated p110fl/fl ROSA-gfp mouse.PLoS One 14, no. 2 (2019): e0212930. https://doi.org/10.1371/journal.pone.0212930.
Guo X, Liu Y, Kim JL, Kim EY, Kim EQ, Jansen A, Li K, Chan M, Keenan BT, Conejo-Garcia J, Lim DC. Effect of cyclical intermittent hypoxia on Ad5CMVCre induced solitary lung cancer progression and spontaneous metastases in the KrasG12D+; p53fl/fl; myristolated p110fl/fl ROSA-gfp mouse. PLoS One. 2019;14(2):e0212930.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2019

Volume

14

Issue

2

Start / End Page

e0212930

Location

United States

Related Subject Headings

  • X-Ray Microtomography
  • Tumor Suppressor Protein p53
  • Solitary Pulmonary Nodule
  • Ribs
  • Proto-Oncogene Proteins p21(ras)
  • Neoplasm Metastasis
  • Myocardium
  • Mice, Transgenic
  • Mice
  • Mediastinum