02 December 2022

Cancer in vitro

Scientists have grown an organoid from human tissue to simulate food tube cancer

Tatiana Matveeva, "Scientific Russia"

Researchers from the USA have grown in the laboratory a three-dimensional model (organoid) of a gastrointestinal junction (gastroesophageal junction, GEJ) obtained from human tissues and turned it into a cancer model, the Johns Hopkins Medicine press center reports. The results of the work presented in the journal Science Translational Medicine (Zhao et al., Generation and multiomic profiling of a TP53/CDKN2A double-knockout gastroesophageal junction organoid model) help to track how food tube cancer begins to develop and reveal a possible biological target for treatment with a drug capable of slowing or stopping the growth of such tumors in mice.

Prior to this, there was no unique model that distinguishes between GEJ junction tumors, where the food tube of the digestive system connects to the stomach. Therefore, this type of cancer is often classified either as esophageal cancer or stomach cancer, and not as GEJ cancer, the authors note. It was difficult to show how the tumor begins to develop at the junction of the stomach and esophagus.

To fix this, a group of researchers created a GEJ cancer model by taking normal tissue from patients using biopsy. Organoids include three—dimensional collections of cells derived from stem cells that can reproduce the properties of an organ or what an organ does - for example, create certain types of cells.

Using CRISPR-Cas9 gene editing technology, the researchers removed two key tumor suppressor genes (TP53 and CDKN2A) in the organoids. The double "knockout" of these genes led to the fact that the cells began to turn into cancerous, grow faster and acquire microscopic features similar to those of a malignant tumor. These altered organoids also formed tumors in mice with immunodeficiency.


In addition, the team found anomalies in lipid molecules that store energy and perform many other functions, and identified platelet activation factor as a key activating lipid in GEJ organoids. Platelets circulate in the bloodstream and bind to each other or clot when they recognize damaged blood vessels, and in some people they can cause blood clotting diseases.

"Combining organoids with this gene editing method [CRISPR/Cas9] is a potentially fruitful strategy for studying other human tumors in general," the authors say.

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