Lung Cancer Cells Lose Malignancy in Normal Embryonic Environments

Using lung cancer cell lines, researchers in Barcelona have shown that the same molecular signals that control embryonic development can also influence the harmfulness of cancer cells—findings that could lead to lung cancer treatments that don’t rely on cell death. 

Lung embryonic development involves cell signals that regulate proper formation and differentiation of the organ. Several studies have also confirmed that the abnormal expression of the genes in charge of this embryonic development can cause tumor growth. The researchers hypothesized that the characteristics and malignant activity of lung cancer cells could become more benign in contact with a normal embryonic lung microenvironment.

“In this study, we observed that lung cancer cells, when cultured in a human embryonic lung mesenchyme-conditioned medium, lose the malignant phenotype, their morphology changes and they inhibit their in vivo and in vitro proliferation,” says Mariano Monzó, emeritus professor of Anatomy and Human Embryology at the Faculty of Medicine and Health Sciences of the University of Barcelona.

The researchers monitored two cell lines of non-small lung cancer cells to evaluate which morphological, functional and molecular changes occurred in an embryonic culture medium. They also evaluated the differences between the formation of tumors and the growth of cells when implanted in mice to evaluate evolution in vivo. The cells showed reduced abilities in proliferation, migration, and formation of colonies, and in vivo tumor growth was also reduced.

Specifically, they found inhibition of pluripotency factors (OSKM) and oncogenic factors (NKX2.1), and a differentiation and reduction of the tumoral proliferation.  By contrast, the cancer cells cultured in a tumoral cancer medium kept their morphology and cancer evolution.

 Current therapies to fight lung cancer and solid tumors in general rely on inducing apoptosis, or programmed death, of cancer cells. These therapies have toxicity issues and can lead to treatment resistance. The results of this study suggest a new approach based on reducing self-replication of lung cancer cells using embryonic factors secreted during lung development.

 “The next step would be to solve which are the molecular pathways and the embryonic lung factors involved in the control of the differentiation of cancer cells we have observed in the study,” the authors say. “Once we define the pathways and factors involved in the differentiation process, we have to validate their use as targets to get a future complementary treatment for lung cancer.”

The results of the study were published in the Journal of Experimental & Clinical Cancer Research.