What stem cells have to do with stomach cancer
The surface of the stomach is lined by a delicate single-layered sheet of epithelial cells (termed the gastric mucosa and its glands), which represents a tight barrier to the outside world (i.e., the gastric juice and its contents including a variety of microorganisms, such as Helicobacter pylori) and is also essential for the digestion of food. The stomach consists of two major parts (Fig. 1), a proximal fundus/corpus region with fundic glands producing the gastric acid, and the distal antrum with antral glands releasing the peptide hormone gastrin. During evolution, a series of protection and repair mechanisms have been developed because the gastric mucosa is permanently exposed to different noxious agents. These mechanisms include the formation of a complex mucous gel containing mucins, secretion of antimicrobial peptides, acute inflammatory processes, rapid repair by cell migration (restitution) within minutes to hours, and continual self-renewal of the various cell types by differentiation from progenitor cells and adult (somatic) stem cells (Fig. 1). The latter process takes days to months depending on the cell type.
Only within the last few years it has become clear that gastric glands contain an unexpected variety of stem cell populations, which are even different in fundic and antral glands (Fig. 1). Of note, the isthmus is no longer thought to serve as the exclusive stem cell reservoir. Thus far, the relation and the hierarchy, respectively, between the different gastric stem cell (GSC) populations in a single gastric unit have not been established.
Some 90% of primary tumors in adult humans arise from epithelia mainly on the base of chronic inflammation because of their high regenerative capacity and the existence of adult stem cells. Gastric cancer is still a leading cause of cancer-related mortality worldwide (10% of total cancer deaths in 2008) in spite of declining incidence. Gastric cancers are essentially adenocarcinomas (90%) and 50% of these epithelial tumors are classified histologically as the “intestinal” type. Gastric cancer is promoted by environmental factors such as smoked meat, chilli peppers, alcohol, and smoking. However, the most striking risk factor is infection with H. pylori causing chronic inflammation (gastritis). For the intestinal type of adenocarcinomas, a well-defined sequence of events (the “Correa cascade”) has been known for a long time, starting from chronic gastritis and proceeding to gastric atrophy (loss of parietal and zymogenic cells), intestinal metaplasia (aberrant occurrence of intestinal cells in the stomach), and dysplasia. Within the last years it turned out that also a second type of metaplasia (the “spasmolytic polypeptide-expressing metaplasia”/SPEM) is involved in gastric carcinogenesis.
Tumors consist of a heterogeneous, hierarchical population of cancer cells. Importantly, only cancer stem cells (CSCs) can initiate tumor formation. Thus, CSC-targeted therapies might be promising future strategies to cure gastric cancer. Currently, there are three origins of gastric CSCs discussed, i.e., (i) dedifferentiation of metaplasias, (ii) transformation of normal adult GSCs, and (iii), to a lesser extent, engraftment of bone marrow-derived mesenchymal stem cells under the conditions of chronic inflammation. Thus, gastric cancer is now regarded as a disease resulting from the dysregulated differentiation of certain stem and progenitor cells mainly due to a chronic inflammatory environment. Understanding the self-renewal of the gastric mucosa is an important contribution in understanding gastric carcinogenesis and in developing new gastric cancer therapies.
Institute of Molecular Biology and Medicinal Chemistry,
Otto-von-Guericke-University Magdeburg, Germany
Current Status on Stem Cells and Cancers of the Gastric Epithelium.
Int J Mol Sci. 2015 Aug
|Structure and function of the esophageal mucosa Structure and function go hand-in-hand amongst the morphology, morphometry, biomechanics and secretory potential within the alimentary tract mucosa, submucosa and muscularis propria. Structure must evolve first during the development of…|
|The woody breast condition affects texture… The wooden breast condition (WBC) is a muscle abnormality observed in chicken breast meat (Pectoralis major) that is an emerging challenge to the poultry industry. Breast meat with the WBC…|
|Building and rebuilding gastric epithelium: Trop2 as… In mammals, the stomach is lined by a contiguous layer of cells called epithelium, further organized into units called glands. Gastric glands are divided into two areas: corpus and antrum,…|
|The importance of immature cancer cells in… The word “cure” for breast or any other type of cancer might be unfair to a patient since this will give the individual a false sense of comfort. The misuse…|
|Combined technology for ready-to-cook meat safety… Meat is a highly perishable product. At its production chain, the physicochemical and microbiological quality of meat can be deteriorated because of the physiological status of the animal at slaughter,…|
|FTIR spectroscopy and ımaging to understand donor… Stem cells, like Bone Marrow Mesenchymal Stem Cells (MSCs), have enormous potential to develop new therapies for tissue regeneration and repair with their ability to differentiate into many different types…|