Abstract

Lung diseases pose the highest risk of death and lung cancer is a top killer among cancers with a mortality rate up to 70% within 1 year after diagnosis. Such a fast escalation of this cancer development makes early diagnosis and treatment a highly challenging task, and currently there are no effective tools to diagnose the disease at an early stage. The ability to discriminate between healthy and tumorous tissue has made autofluorescence bronchoscopy a promising tool for detection of lung cancer; however, specificity of this method remains insufficiently low. Here, we perform autofluorescence imaging of human lung cancer invading a human functional airway using an in vitro model of Non Small Cell Lung Cancer which combines a reconstituted human airway epithelium, human lung fibroblasts and lung adenocarcinoma cell lines, OncoCilAir™. By using two-photon laser induced autofluorescence microscopy combined with spectrally resolved imaging, we found that OncoCilAir™ provides tissue’s health dependent autofluorescence similar as observed in lung tissue in patients. Moreover, we found spectral and intensity heterogeneity of autofluorescence at the edges of tumors. This metabolic related heterogeneity demonstrates ability of tumor to influence its microenvironment. Together, our result shows that OncoCilAir™ is a promising model for lung cancer research.

Highlights

  • Lung diseases pose the highest risk of death and lung cancer is a top killer among cancers with a mortality rate up to 70% within 1 year after diagnosis

  • The respiratory epithelium was reconstituted from primary human airway epithelial cells isolated from patient bronchial tissue samples

  • TM Human lung cancer modeled by OncoCilAir

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Summary

Introduction

Lung diseases pose the highest risk of death and lung cancer is a top killer among cancers with a mortality rate up to 70% within 1 year after diagnosis. Clinical studies of the healthy bronchial wall, and metaplastic and dysplastic bronchial lesions showed a significant decrease in the autofluorescence intensity and red shifted autofluorescence from the lesions compared to healthy bronchial tissues[14,15,16] These differences in fluorescence of healthy and cancerous tissue provides an attractive contrast for the detection of tumors and has triggered the development of autofluorescence bronchoscopy[4,17,18,19]. Autofluorescence methods allows identification of pre-invasive lesions and has potential for postoperative surveillance[22] Treatment of such lesions is expected to significantly increase efficiency in the curing and diagnosis of lung cancer[23,24].

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