<p>The Association Between Inflammation, Epithelial Mesenchymal Transition and Stemness in Colorectal Carcinoma</p>

Abstract

Background: Inflammation plays an important albeit dual role in carcinogenesis. Survival studies have highlighted the prognostic significance of peritumorous inflammation. Currently, the theoretical background allows inflammation, epithelial mesenchymal transition (EMT) and the closely associated stem cell differentiation in colorectal carcinoma (CRC) to be linked. However, there is scarce direct morphological evidence. Purpose and methods: The aim of our study was to investigate the role of inflammation in cancer growth and invasion by analyzing the association between inflammation and known morphological prognostic features of colorectal cancer, EMT, stemness and mismatch repair (MMR) protein expression. The study was designed as a retrospective morphological and immunohistochemical assessment of 553 consecutive cases of surgically treated primary CRC. Results: There were statistically significant associations between high-grade inflammation and lower pT (p = 0.002), absence of lymph node metastases (p < 0.001) and less frequent lymphatic (p = 0.003), venous (p = 0.017), arterial (p = 0.012), perineural (p = 0.001) and intraneural (p = 0.01) invasion. In contrast, Crohn's like reaction (CLR) by density of lymphoid follicles in the invasive front lacked significant differences in regard to pT, pN, tumor invasion into surrounding structures (blood or lymphatic vessels, nerves), grade or necrosis (all p > 0.05). The expression of E-cadherin, CD44 and MMR proteins yielded no statistically significant associations with peritumorous inflammation by Klintrup-Mäkinen score or the density of lymphoid follicles. Nevertheless, E-cadherin levels were significantly associated with the density of eosinophils (p = 0.007). Conclusion: High-grade peritumorous inflammation is associated with beneficial morphologic CRC features, including less frequent manifestations of invasion, and is not secondary to tissue damage and necrosis. CLR is not associated with cancer spread by pTN; this finding indirectly suggests an independent role of CLR in carcinogenesis. Further, inflammation by Klintrup-Mäkinen grade and CLR is not dependent on epithelial-mesenchymal transition and stem cell differentiation. Our study highlights the complex associations between inflammation, tumor morphology, EMT, stemness and MMR protein expression in human CRC tissues.

Stemness, Inflammation and Epithelial–Mesenchymal Transition in Colorectal Carcinoma: The Intricate Network

“…Further, the inherent complexity of tumour tissues can provide the background for redundant regulatory links. The network of these links could outweigh certain linear biological mechanisms evident in controlled in vitro experiments [ 32 ].…”

Research Progress on the Relationship Between Inflammation and Colorectal Cancer

“… 101 The EMT process can stimulate the production of inflammatory factors by cancer cells, 102 and the evidence of its relationship with inflammation in CRC has been fixed. 103 EMT mainly refers to the biological process in which epithelial cells lose their epithelial properties and turn into mesenchymal cells. Its main features are the reorganization of the cell skeleton and the loss of intercellular adhesion.…”

Inflammation Endows Benign Prostatic Hyperplasia Cells With Similar Physical Properties to Prostate Cancer Cells

“…These factors affect the expression of receptor proteins in the cell membrane, activate signaling pathways, and cause changes in cell membrane folding and protrusion [35] [2], which induce the increase of SMC value. Another potential key factor in the relationship between inflammation and PCa is the expression of transforming growth factor beta, which has been found at increased levels in prostates with inflammation and might be involved in the epithelial-mesenchymal transition (EMT) [36]. The EMT is often accompanied with changes of mechanical properties.…”