Abstract
We studied the in-vitro/. in-vivo interactions between HCC/HSCs in early and advanced fibrosis-models. Hep3B-mono-cultures secreted high levels of αFetoProtein (αFP). Human-HSCs co-cultured with Hep3B-cells significantly decreased αFP and increased their apoptosis. Confocal-microscopy demonstrated Hep3B-phagocytosis inside the HSCs suggesting a direct cellular-contact mediating anti-tumor effect. Leptin-activated HSCs further suppressed Hep3B-cells with increased ROS and decreased GSH. Following intrahepatic-Hep3B-cell injections, mice with established "advanced liver-fibrosis"; had higher tumor-size and αFP serum-levels as compared to non-fibrotic livers. Mice with "early liver-fibrosis", which initiated post tumor induction had a significant decrease in tumor and high Malondialdehyde (MDA) serum levels compared to advanced-fibrosis animals.At early-fibrosis stages, activated-HSCs express direct anti-tumor effects by phagocytosis and apoptosis of tumor-cells mediated by oxidative stress.
| Original language | English |
|---|---|
| Pages (from-to) | 391-398 |
| Number of pages | 8 |
| Journal | Mitochondrion |
| Volume | 13 |
| Issue number | 5 |
| DOIs | |
| State | Published - Sep 2013 |
| Externally published | Yes |
Bibliographical note
Funding Information:This study was supported (in part) by grant no. 35937 from the Chief Scientist Office of the Ministry of Health, Israel and by the Israel Science Foundation grant no. 1169/09 .
Funding
This study was supported (in part) by grant no. 35937 from the Chief Scientist Office of the Ministry of Health, Israel and by the Israel Science Foundation grant no. 1169/09 .
| Funders | Funder number |
|---|---|
| Israel Science Foundation | 1169/09 |
| Ministry of Health, State of Israel |
Keywords
- Cirrhosis
- Free radicals
- Hep3B cells
- Hepatic fibrosis
- Homeostasis
- Phagocytosis