Tumour microenvironment: a non-negligible driver for epithelial−mesenchymal transition in colorectal cancer

Abstract

Cancer remains the leading cause of death worldwide, and metastasis is still the major cause of treatment failure for cancer patients. Epithelial–mesenchymal transition (EMT) has been shown to play a critical role in the metastasis cascade of epithelium-derived carcinoma. Tumour microenvironment (TME) refers to the local tissue environment in which tumour cells produce and live, including not only tumour cells themselves, but also fibroblasts, immune and inflammatory cells, glial cells and other cells around them, as well as intercellular stroma, micro vessels and infiltrated biomolecules from the nearby areas, which has been proved to widely participate in the occurrence and progress of cancer. Emerging and accumulating studies indicate that, on one hand, mesenchymal cells in TME can establish ‘crosstalk’ with tumour cells to regulate their EMT programme; on the other, EMT-tumour cells can create a favourable environment for their own growth via educating stromal cells. Recently, our group has conducted a series of studies on the interaction between tumour-associated macrophages (TAMs) and colorectal cancer (CRC) cells in TME, confirming that the interaction between TAMs and CRC cells mediated by cytokines or exosomes can jointly promote the metastasis of CRC by regulating the EMT process of tumour cells and the M2-type polarisation process of TAMs. Herein, we present an overview to describe the current knowledge about EMT in cancer, summarise the important role of TME in EMT, and provide an update on the mechanisms of TME-induced EMT in CRC, aiming to provide new ideas for understanding and resisting tumour metastasis.

Oxidized low-density lipoprotein stimulates CD206 positive macrophages upregulating CD44 and CD133 expression in colorectal cancer with high-fat diet

“…Existing clinical studies have reported that the CD206+ macrophage level is positively correlated with the TNM stage, the number of metastasized lymph nodes, and the degree of vascular invasion[ 22 ], and high CD206+ macrophage expression suggests a poor prognosis. Han et al [ 11 ] found that CD206+ macrophages in the tumor microenvironment could promote CRC metastasis through interaction with CRC cells. CD206+ macrophages have been reported to be elevated in colorectal tissues in patients with hyperlipidemia.…”

“…An increasing body of evidence suggests that CD206+ macrophages in the tumor microenvironment promote CRC development, and a positive correlation has been documented between the level of CD206+ macrophages and the degree of tumor malignancy[ 10 ]. Moreover, metastasis can be promoted through the interactions of CD206+ macrophages with CRC cells[ 11 ]. Liu et al [ 7 ] found that the prevalence of CRC was higher in people on a HFD with upregulated CD206+ macrophage levels in colon tissue.…”

Immune micro-environment and drug analysis of peritoneal endometriosis based on epithelial-mesenchymal transition classification

“…The migration and invasion abilities of endometrial stromal cells enhanced by facilitated EMT, and conversely inhibited EMT-related proteins reduced the volume and weight of endometriotic lesions in mice model ( 43 – 45 ). In pathological and physiological EMT, both stroma cells and immune cells are involved ( 46 – 48 ). Researches concerning stroma cell involve in EMT are not rare.…”

Curcuminoids as Modulators of EMT in Invasive Cancers: A Review of Molecular Targets With the Contribution of Malignant Mesothelioma Studies

“…In addition to Hippo/yap, nuclear factor-kappa B (NF-κB), janus kinases/signal transducer and activator of transcription proteins (JAK/STAT), mitogen-activated protein kinases (MAPK), and phosphatidylinositol 3-kinase (PI3K)/Akt/ mechanistic target of rapamycin (mTOR), investigations on each of these pathways have been the subject of new developments in the last 3 years and are reviewed below. Meanwhile, the role of potential additional factors that drive EMT in cancer (Figure 2) was also highlighted, namely transcriptional factors (TFs) (Vishnoi et al, 2020), translation initiation mechanisms (Bera and Lewis, 2020), miRNAs (Pan et al, 2021) and circular RNAs (circRNAs) (Jiang M. et al, 2021), hypoxia (Peng P. H. et al, 2021), inflammation (Chattopadhyay et al, 2021, and stromal components like tumor-associated macrophages (TAMs) (Han et al, 2021) and cancer-associated fibroblasts (CAFs) (Asif et al, 2021). Other emerging or developing research fields were represented by cancer-associated adipocytes (Liu et al, 2020), endothelial cells and their transformation via endothelial-tomesenchymal transition (EndMT) (Yoshimatsu and Watabe, 2022), and vascular mimicry (Sun et al, 2017).…”