Abstract 290P
Background
Smoking is a high-risk factor for lung cancer due to the carcinogens in tobacco, contributing to all histological types of lung cancer and being the leading cause of mortality among lung cancer patients. To improve prevention, diagnosis, and treatment of smoking-induced lung cancer, we aimed to develop a comprehensive smoking-lung cancer model, overcoming the limitations of traditional 2D in vitro models by incorporating animal studies and microfluidic technology.
Methods
The A549-CSE cell line was established by exposing A549 cells to cigarette smoke extract (CSE), creating a smoking-lung cancer model. Cell viability, migration, and invasion capacities of A549-CSE were assessed through 2D cultures. Spheroids generated from A549 and A549-CSE cells were transplanted into mice for in vivo analysis. Tumor progression markers were evaluated through real-time PCR andWestern blotting. Additionally, a microfluidic chip was used to assess the invasion capacity of A549-CSE cells.
Results
A549-CSE cells demonstrated increased viability, migration, and invasion in 2D culture. Genetic and protein analysis revealed enhanced expression of mesenchymal markers (N-cadherin, vimentin), beta-catenin, and snail, an EMT inducer, while epithelial marker E-cadherin showed no significant change. In animal models, A549-CSE spheroid transplantation resulted in significantly larger tumors compared to controls. On a microfluidic chip, A549-CSE cells exhibited heightened invasive properties, confirming their tumor-promoting characteristics.
Conclusions
The study highlights smoking as a key contributor to the tumor microenvironment and demonstrates the utility of the A549-CSE smoking-lung cancer model for studying cancer progression. This model provides valuable insights for the prevention, diagnosis, and treatment of lung cancer associated with smoking.
Funding
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (NRF-2021R1A2C2009932 and NRF-2022R1I1A1A01063972).
Disclosure
All authors have declared no conflicts of interest.