Translational Significance for Tumor Metastasis of Tumor-Associated Macrophages and Epithelial–Mesenchymal Transition

Abstract

The tumor microenvironment determines development and progression of many cancers. Epithelial–mesenchymal transition (EMT) is fundamental to tumor progression and metastasis not only by increasing invasiveness but also by increasing resistance to cell death, senescence, and various cancer therapies; determining inflammation and immune surveillance; and conferring stem cell properties. It does this by enabling polarized epithelial cells to transform into cells with a mesenchymal, and therefore motile, phenotype. Tumor-associated macrophages (TAMs) are key cells of the tumor microenvironment that orchestrate the connection between inflammation and cancer. Activation of EMT often requires crosstalk between cancer cells and components of the local tumor microenvironment, including TAMs. In this review, clinical and experimental evidence is presented for control of TAMs in promoting cancer cell invasion and migration and their interaction with the EMT process in the metastatic cascade. The translational significance of these findings is that the signaling pathways that interconnect TAMs and EMT-modified cancer cells may represent promising therapeutic targets for the treatment of tumor metastasis.

RETRACTED ARTICLE: Long non-coding XIAP-AS1 regulates cell proliferation, invasion and cell cycle in colon cancer

“…Modification of the cell cycle has been considered as an important therapeutic strategy for colon cancer treatment [20]. The current study demonstrates that silencing of XIAP-AS1 causes G0/G1 phase cell-cycle arrest via downregulation of cyclin D1, cyclin E, and c-Myc levels, which appears to be the underlying mechanism in colon cancer cell growth inhibition As a critical mechanism of tumour metastasis [22], EMT has been shown to be involved in the aggressive tumour biology of a variety of cancers, including colon cancer [23]. During the process of EMT, cells lose their cellular epithelial features and gain mesenchymal properties with increased migration and invasion abilities, which can invade and migrate through the body [24].…”

Role of the NFκB-signaling pathway in cancer

“…NFκB signaling is involved in cellular immunity, inflammation, and stress, as well as regulation of cell differentiation, proliferation, and apoptosis. 97 – 101 The NFκB pathway is often altered in both solid and hematopoietic malignancies, promoting tumor-cell proliferation and survival. 52 , 102 , 103 However, recent evidence indicates that NFκB plays a tumor-suppressive role in certain cancers through transcriptional activation of the Fas ligand.…”

Circulating ensembles of tumor‐associated cells: A redoubtable new systemic hallmark of cancer

“…However, EpCAM‐based approaches are not suitable for identification of CTCs that have undergone epithelial to mesenchymal transition . EpCAM‐based approaches also have limited efficacy in isolation of heterotypic C‐ETACs for the same reason: EpCAM+ cells in viable C‐ETACs can be obscured from detection due to sequestration with a plethora of cells such as post‐EMT CTCs, tumor‐associated T‐lymphocytes (TAL), TAM and CSCs . The C‐ETAC isolation process used in our approach is neither microfluidic nor epitope‐based and is hence unaffected by the limitations of the respective approaches.…”