Researchers have found the mechanism responsible for the development of cancer-associated fibroblasts which are essential to lung adenocarcinoma.
Lung adenocarcinoma is a common form of lung cancer. The cancer cells associated with lung adenocarcinoma contribute to all the phases of tumour development, including metastasis.
The study was a collaborative effort project made up of researchers from the University of Barcelona, the University of Zaragoza, and Hospital Clínic de Barcelona. The findings have been published in the British Journal of Cancer.
The findings will facilitate the development of new anti-cancer drugs
The study has enabled researchers to explore the development of an inhibitor drug which could be used to combat the migratory advantage of these lung adenocarcinoma-associated cells, preventing their contribution to tumour development.
“The importance of these findings lies in the fact that lung adenocarcinoma represents 40% of the cases of lung cancer and it produces an early metastasis, which directly affects the patient’s chances of survival,” said lecturer Jordi Alcaraz, coordinator of the study and member the Institute of Bioengineering of Catalonia.
The five-year survival rate for lung cancer that has not spread to other organs is currently just over 60%. However, if the disease other parts of the body, the survival rate is reduced to below 10%.
The role SMAD3 proteins in tumour development
Previous studies have shown that the SMAD3 protein is overactivated in lung adenocarcinoma patients. This study analysed the effects of the SMAD3 protein in cancer-associated cell development and examined its impact on tumour dissemination and metastasis generation.
The team used innovative technology based on microfluidic devices with 3D collagen extracellular matrices to analyse the protrusions and migration of cancer cells in environments that simulated different stages of tumour growth.
Cancer-associated cells were faster and more direct in movement in environments similar to the early stages of cancer. The researchers also observed a lower proliferative capacity in these cells. The cells used the SMAD3 protein as an essential factor in the development and accumulation of fibroblasts in lung adenocarcinoma.
As cancer-associated cells are important in all four stages of tumour development, these findings could be important in understanding the early dissemination of lung adenocarcinoma to other organs.
As well as this, the migratory advantage was removed by the inhibitor Trametinib, which has already been approved for use in other types of tumours, suggesting it could be used in lung adenocarcinoma treatment.
“We found that the adenocarcinoma tumour-associated cells have a high migratory capacity. This enables their recruitment to the tumour more easily, and it could favour an early metastasis formation, a process observed in patients but for which the causes are still unknown. In addition, inhibitors such as Trametinib, according to our results, could be effective against recruitment,” explained Yago Juste Lanas, first author of the study.
In environments similar to that of developed tumours, researchers said that lung adenocarcinoma-associated cells established closer interactions with tumour cells due to the reduction of the migratory capacity.
“We continue to work to understand whether lung adenocarcinoma-associated cells can also promote the spread of these tumours by other mechanisms, with the ultimate aim of curbing their metastasis,” concluded Lanas.