Researchers from Weill Cornell Medicine have used human embryonic stem cells to create a new model system that allows them to study the initiation and progression of small cell lung cancer (SCLC). The study, which will be published February 8 in the Journal of Experimental Medicine, reveals the distinct roles played by two critical tumor suppressor genes that are commonly mutated in these highly lethal cancers.
SCLC is thought to develop from a particular type of lung cell, called pulmonary neuroendocrine cells (PNECs), but until now, no one knew how to induce human embryonic stem cells to become PNECs in the lab. “We discovered a means to induce pulmonary neuroendocrine-like cells from cultured human embryonic stem cells after first differentiating them into lung progenitor cells,” says Huanhuan Joyce Chen, a postdoctoral fellow at the Meyer Cancer Center, Weill Cornell Medicine, who was one of the lead authors on the study. “We did this by blocking an important cell signaling pathway known as the NOTCH pathway.”
“Our system should enable further studies of the progression of these early-stage tumors into invasive SCLCs that resemble the more aggressive cancers found in patients,” says Harold Varmus, co-lead author of the study and Lewis Thomas University Professor at Weill Cornell Medicine. “If so, it should be possible to test cells at different stages of tumor development for susceptibility and resistance to therapeutic strategies.”
Huanhuan Joyce Chen et al. Generation of pulmonary neuroendocrine cells and SCLC-like tumors from human embryonic stem cells. JEM, 2019 DOI: 10.1084/jem.20181155