Hepatic metastatic niche: from normal to pre-metastatic and metastatic niche

Abstract

Liver is the organ responsible for hematopoiesis during fetal life, which is also a target organ of metastasis for several cancers. In order to recognize the hepatic metastatic changes, obtain a better grasp of cancer prevention, treatment, and inhibition mode of hepatic metastasis progression, we investigate the changes and transformation of normal hepatic niche cells to metastatic niche ones in this review. On the other hand, since metastatic diseases alter the liver function, the changes in a number of cancers that metastasize to the liver have also been reviewed. Relevant English-language literature was searched and retrieved from PubMed (1994-2014) using the following keywords: hepatic stem cell niche, hepatic metastatic niche, chemokine, and microRNAs (miRNAs). Also, over 86 published studies were investigated, and bioinformatics analysis of differentially expressed miRNAs in hepatic cancer and metastasis was performed. Metastasis is developed in several stages with specific changes and mechanisms in each stage. Recognition of these changes would lead to detection of new biomarkers and clinical targets involved in specific stages of liver metastasis. Investigation of the hepatic stem cell niche, development of metastasis in liver tissue, as well as changes in chemokines and miRNAs in metastatic hepatic niche can significantly contribute to faster detection of liver metastasis progression.

Extracellular Matrix Alterations in Metastatic Processes

“…Major alterations of ECM composition related to metastatic niche formation involve a number of proteins with different roles: the cell-adhesion molecule carcinoembryonic antigen (CEA), cell adhesion molecules (CAMs), CXC motif-chemokines (CXCLs), VEGF, MAPK, NF-κB, Citrullinated proteins/PAD, Spermine pullulan, MMPs and collagen isoforms and these alterations may vary dependently from the originating primary tumor [85].…”

Critical steps to tumor metastasis: alterations of tumor microenvironment and extracellular matrix in the formation of pre-metastatic and metastatic niche

“…In metastasis to liver, excessive TIMP-1 leads to binding of SDF-1, triggering inflammation and further immunocompromise as a part of modification. [34,35]. Moreover, in infiltration to brains, blood-brain barrier's (BBB) physical structure could be disturbed through a triggered inflammatory response, making CTCs easier to break through.…”

Engineering the pre-metastatic niche

“…Different types of metastasizing cancers have preferences for specific organ targets, implying that certain types of cancer are more likely to migrate to and flourish in specific microenvironments 132 – 134 . Metastatic breast cancer cells often populate metastatic niches located at the lungs 135 , liver 136 , brain 137 , bone 138 , and lymph nodes 139 , with each tissue featuring various characteristics that promote tumour cell homing, adhesion, and growth. Aberrantly accumulated proteins produced by tumour-subverted stroma (including organ fibroblasts and endothelial cells) such as fibronectin, collagen IV, tenascin, and periostin promote tumour cell adhesion at metastatic sites 107 , 140 .…”