Loss of PTEN Signaling in Foxl1+ Mesenchymal Telocytes Initiates Spontaneous Colonic Neoplasia in Mice

Telocytes: An Emerging Component of Stem Cell Niche Microenvironment

“…On the basis of the aforementioned intriguing roles proposed for TCs in the digestive tract, a growing number of studies have investigated their possible involvement in different gastrointestinal pathological processes. 25,26,[126][127][128][129][130] Changes in the distribution of TCs have been first reported in surgical specimens obtained from patients affected by Crohn's disease (CD) and UC, two inflammatory bowel diseases characterized by chronic inflammation, extensive tissue fibrosis, and gastrointestinal dysmotility. 126,127 In the terminal ileum of patients suffering from CD, in which fibrosis commonly involves the entire bowel wall and the most peculiar histopathological feature is represented by discontinuous signs of inflammation and fibrosis referred to as "skip lesions," TCs displayed a similar distribution to normal control specimens in disease-unaffected segments, whereas they were significantly reduced in disease-affected portions, particularly in the areas displaying the most severe fibrotic changes and derangement of the intestinal wall architecture.…”

“…8,11,132 As far as cancer is concerned, it has been recently shown that loss of PTEN signaling in Foxl1 + TCs is sufficient to initiate spontaneous colonic neoplasia in mice. 129 Finally, although most authors support the notion that gastrointestinal stromal tumors (GISTs) derive exclusively from or differentiate toward the ICC lineage, a hypothesis corroborated by the fact that they frequently express the c-kit/CD117 antigen, the existence of PDGFRα-mutant GISTs or familial PDGFRα-mutation syndromes has been recently demonstrated, suggesting that PDGFRα + TCs also may be related to this kind of pathological conditions. 26,128…”

Tumor-associated telocytes

“…Immunohistochemical and immunofluorescent staining for biomarkers such as cluster of differentiation 34 (CD34) and platelet-derived growth factor receptor alpha (PDGFRA) can be used to identify TCs in cancer tissues, while negative expression for CD31 and vimentin helps differentiate TCs from other cell types. [ 12 ] However, due to the widespread gene mutations in the TME, TCs may inconsistently express aberrant stem cell markers, necessitating specific biomarkers for different organs and tissues to accurately identify TCs. A significant change is that TCs in the normal vascular wall, which express CD34, have the ability to transform into TCs expressing CD68 and matrix metalloproteinase-9 (MMP9) during tumor angiogenesis and proliferation processes.…”

“…Additionally, a unique- Cre transgenic mouse model verified that Foxl-1 positive TCs were the essential origin of intestinal stem cell niche factors, and Foxl-1 + TCs could be easily observed in the gastrointestinal system. [ 12 , 18 ] It was also discovered that telocyte–phosphatase and tensin homolog (PTEN) signaling is a vital independently protective pathway inhibiting the colonic polyposis proliferation, the PTEN-deficiency signaling in Foxl-1 + TCs was confirmed to accelerate the colonial neoplasia in a mouse model. Those innovative findings will benefit understanding of TATCs in GI cancer.…”