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Hepatic stellate cells: Partners in crime for liver metastases?
Author(s) -
Kang Ningling,
Gores Gregory J.,
Shah Vijay H.
Publication year - 2011
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.24384
Subject(s) - hepatic stellate cell , cancer research , tumor microenvironment , myofibroblast , hepatology , growth factor , transforming growth factor , metastasis , biology , medicine , cancer , receptor , fibrosis , tumor cells
Hepatic stellate cells (HSCs) were recently postulated as a component of the prometastatic liver microenvironment, because they can transdifferentiate into highly proliferative and motile myofibroblasts that are implicated in the desmoplastic reaction and metastatic growth. This review focuses on bidirectional interactions between tumor cells and HSCs in the liver microenvironment and discusses mechanisms whereby tumor‐derived factors activate HSCs, and in turn, activated HSCs promote metastatic growth. Bidirectional interactions between tumors and HSCs may function as an “amplification loop” to further enhance metastatic growth in the liver. The activation of HSCs is a complex process regulated by multiple factors such as transforming growth factor‐β and platelet‐derived growth factor signaling pathways, which may present as therapeutic targets in the prevention and treatment of liver metastases. Conclusion: HSCs may present a new therapeutic target in the treatment of liver metastases. Targeting HSCs and/or myofibroblasts with transforming growth factor‐β or platelet‐derived growth factor antagonists in coordination with chemotherapy, radiotherapy, or surgery may prove to be effective at reducing liver metastases and increasing the survival benefit of patients by targeting both tumor cells and the tumor microenvironment. (H EPATOLOGY 2011;)