Nat commun: revealing the key role of stem cells in lethal gastric cancer

January 16, 2020 / BIOON / -- recently, in a research report published in the international journal Nature communications, scientists from Cornell University made new discoveries in the study of common and fatal gastric cancer In the United States, the incidence of gastroesophageal cancer increased by 2.5 times from the 1970s to the early 21st century However, since the 1950s, the number of all gastric cancer patients has decreased by more than 80% Nevertheless, gastric cancer is still the fifth most common cancer in the world and the third leading cause of cancer death Photo source: in NIH study, researchers identified a new pathway in gastroesophageal cancer, which may be a potential target to help develop new therapies; a group of stem cell progeny named Lgr5 + may gather in large numbers to promote cancer in the place where two gastric tissues meet Professor Alexander nikitin, researcher, said that at the global level, gastric squamous columnar junction cancer (gastroesophageal cancer) is a frequent disease with poor prognosis, so it is very important for patients to study the mechanism of the formation of such cancer and how to treat it In this study, the researchers developed an experimental mouse model with two tumor suppressor genes, which can be inactivated under specific conditions This model meets a number of parameters necessary for accurate cancer research Previously, the researchers had certain limitations on mice, that is, mice Jinhui produced specific types of tumors Early death may occur, which undoubtedly inhibited the study, but in this study, the mouse model developed by the researchers was able to develop the related form of metastatic gastric squamous columnar junction cancer Previous studies have found that Lgr5 + stem cells are involved in many types of cancer, said researcher nikitin This study shows that this may not be applicable to all types of cancer, but there is no evidence that Lgr5 + stem cells themselves can induce gastric squamous columnar junction cancer In this study, researchers used mouse models and organ like organs to study, and found that a large number of offspring named lgr5-cd44 + cells (not Lgr5 + stem cells) would gather at the junction when the stem cells At the time of classification, they will differentiate into specialized cells, but in the early stage of division, these cells are not mature, they have not yet differentiated, and researchers can detect the presence of these progeny cells in the earliest recognizable lesions and advanced cancers After using organ like research, researchers found that these cells will be very easy to transform The results show that the cancer prone characteristics of other transitional zones may also be caused by the presence of a large number of immature cells The researchers also revealed a special protein called osteopontin, which can bind to the receptor of CD44 + cells and open a series of downstream effects The combination of osteopontin-cd44 + can control the relationship between stem cells and differentiated cells Balance, and produce more stem cells and cells with stem cell characteristics, such as lgr5-cd44 + cells The presence of osteopontin signaling can keep cells in an immature state, which may be one of the key mechanisms to explain why the body has a large number of immature cell banks (lgr5-cd44 + cells), the researchers said After studying the two groups of human patients, the researchers found that the results were consistent with those obtained in the mouse model, that is, the low level of osteopontin and CD44 cells were directly related to the higher survival status of the patients, while the late overexpression was directly related to the poor prognosis of the patients with squamous columnar junction cancer of the human stomach Later researchers need to conduct more in-depth research to investigate and analyze whether osteopontin inhibitors and CD44 + cell antibodies can be used to inhibit the accumulation of lgr5-cd44 + cells, so as to better treat cancer Original source: Fu, D., Wang, L., chouairi, f.k et al Gastric squamous column junction contains a large pool of cancer prone immaterial responsible Lgr5 − CD44 + cells NAT commun 11, 84 (2020) doi: 10.1038/s41467-019-13847-2