UNLABELLED: 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.
UNLABELLED: 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.
Authors: Vidya Ganapathy; Rongrong Ge; Alison Grazioli; Wen Xie; Whitney Banach-Petrosky; Yibin Kang; Scott Lonning; John McPherson; Jonathan M Yingling; Swati Biswas; Gregory R Mundy; Michael Reiss Journal: Mol Cancer Date: 2010-05-26 Impact factor: 27.401
Authors: T Torimura; M Sata; T Ueno; M Kin; R Tsuji; K Suzaku; O Hashimoto; H Sugawara; K Tanikawa Journal: Hum Pathol Date: 1998-09 Impact factor: 3.466
Authors: Yue Guo; Zheng-Yuan Su; Chengyue Zhang; John M Gaspar; Rui Wang; Ronald P Hart; Michael P Verzi; Ah-Ng Tony Kong Journal: Biochem Pharmacol Date: 2017-03-04 Impact factor: 5.858
Authors: Chunsheng Liu; Daniel D Billadeau; Haitham Abdelhakim; Edward Leof; Kozo Kaibuchi; Carmelo Bernabeu; George S Bloom; Liu Yang; Lisa Boardman; Vijay H Shah; Ningling Kang Journal: J Clin Invest Date: 2013-02-01 Impact factor: 14.808