Article first published online: 25 JUL 2011
Copyright © 2011 American Association for the Study of Liver Diseases
Volume 54, Issue 2, pages 707–713, August 2011
How to Cite
Kang, N., Gores, G. J. and Shah, V. H. (2011), Hepatic stellate cells: Partners in crime for liver metastases?. Hepatology, 54: 707–713. doi: 10.1002/hep.24384
Potential conflict of interest: Nothing to report.
Supported by The Howard Temin Award (K01 CA), 2009 Research Early Career Development Award (Mayo Clinic), and P/F Award (P30 NIDDK Center Grant) (to N.K.), DK59615 (to V.S.), and DK59427 (to G.G.).
- Issue published online: 25 JUL 2011
- Article first published online: 25 JUL 2011
- Accepted manuscript online: 21 APR 2011 01:16PM EST
- Manuscript Accepted: 13 APR 2011
- Manuscript Received: 1 MAR 2011
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. (HEPATOLOGY 2011;)