Abstract
Backgrounds & Aims: Cholangiocarcinoma (CCA) is highly fatal because of early invasion, widespread metastasis, and lack of an effective therapy. Migration, invasion, and metastasis of CCA cells are modulated by signals received from stromal cells. The SDF-1-CXCR4 axis emerges as a pivotal regulator of migration and survival of different tumor cells. The aim of the present study was to characterize the interaction between CCA cells and human hepatic stellate cells (hHSC) focusing on the role of SDF-1. Methods: The intrahepatic CCA cell line HuCCT-1 and primary hHSC were used for this study. RNA expression was examined by RTQ-PCR and protein expression by Western blotting. Immunofluorescence microscopy and immunohistochemistry were also employed. Migration of CCA cells was assessed using modified Boyden chambers. Results: CXCR4 was clearly expressed in CCA cells of human CCA liver specimens. SDF-1 and hHSC conditioned medium (CM) promoted HuCCT-1 cell migration, which was abrogated by pre-incubation with AMD3100, a non-peptide antagonist of the CXCR4 receptor. In addition, HuCCT-1 cells silenced for CXCR4 did not migrate in presence of SDF-1. Both P-ERK and p-AKT were implicated in HuCCT-1 migration and showed a biphasic trend under stimulation of SDF-1. Finally, SDF-1 induced apoptotic rescue of HuCCT-1 cells by binding to CXCR4. Conclusions: Our study demonstrates that CCA cells migration and survival are modulated by the crosstalk between SDF-1, released by hHSC, and HuCCT-1 cells bearing CXCR4.
| Original language | English |
|---|---|
| Pages (from-to) | 813-820 |
| Number of pages | 8 |
| Journal | Journal of Hepatology |
| Volume | 57 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Oct 2012 |
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Keywords
- Cholangiocarcinoma
- HuCCT-1 migration
- HuCCT-1 survival
- SDF-1/CXCR4 axis
ASJC Scopus subject areas
- Hepatology
Cite this
Role of the stromal-derived factor-1 (SDF-1)-CXCR4 axis in the interaction between hepatic stellate cells and cholangiocarcinoma. / Gentilini, Alessandra; Rombouts, Krista; Galastri, Sara; Caligiuri, Alessandra; Mingarelli, Eleonora; Mello, Tommaso; Marra, Fabio; Mantero, Stefano; Roncalli, Massimo; Invernizzi, Pietro; Pinzani, Massimo.
In: Journal of Hepatology, Vol. 57, No. 4, 10.2012, p. 813-820.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Role of the stromal-derived factor-1 (SDF-1)-CXCR4 axis in the interaction between hepatic stellate cells and cholangiocarcinoma
AU - Gentilini, Alessandra
AU - Rombouts, Krista
AU - Galastri, Sara
AU - Caligiuri, Alessandra
AU - Mingarelli, Eleonora
AU - Mello, Tommaso
AU - Marra, Fabio
AU - Mantero, Stefano
AU - Roncalli, Massimo
AU - Invernizzi, Pietro
AU - Pinzani, Massimo
PY - 2012/10
Y1 - 2012/10
N2 - Backgrounds & Aims: Cholangiocarcinoma (CCA) is highly fatal because of early invasion, widespread metastasis, and lack of an effective therapy. Migration, invasion, and metastasis of CCA cells are modulated by signals received from stromal cells. The SDF-1-CXCR4 axis emerges as a pivotal regulator of migration and survival of different tumor cells. The aim of the present study was to characterize the interaction between CCA cells and human hepatic stellate cells (hHSC) focusing on the role of SDF-1. Methods: The intrahepatic CCA cell line HuCCT-1 and primary hHSC were used for this study. RNA expression was examined by RTQ-PCR and protein expression by Western blotting. Immunofluorescence microscopy and immunohistochemistry were also employed. Migration of CCA cells was assessed using modified Boyden chambers. Results: CXCR4 was clearly expressed in CCA cells of human CCA liver specimens. SDF-1 and hHSC conditioned medium (CM) promoted HuCCT-1 cell migration, which was abrogated by pre-incubation with AMD3100, a non-peptide antagonist of the CXCR4 receptor. In addition, HuCCT-1 cells silenced for CXCR4 did not migrate in presence of SDF-1. Both P-ERK and p-AKT were implicated in HuCCT-1 migration and showed a biphasic trend under stimulation of SDF-1. Finally, SDF-1 induced apoptotic rescue of HuCCT-1 cells by binding to CXCR4. Conclusions: Our study demonstrates that CCA cells migration and survival are modulated by the crosstalk between SDF-1, released by hHSC, and HuCCT-1 cells bearing CXCR4.
AB - Backgrounds & Aims: Cholangiocarcinoma (CCA) is highly fatal because of early invasion, widespread metastasis, and lack of an effective therapy. Migration, invasion, and metastasis of CCA cells are modulated by signals received from stromal cells. The SDF-1-CXCR4 axis emerges as a pivotal regulator of migration and survival of different tumor cells. The aim of the present study was to characterize the interaction between CCA cells and human hepatic stellate cells (hHSC) focusing on the role of SDF-1. Methods: The intrahepatic CCA cell line HuCCT-1 and primary hHSC were used for this study. RNA expression was examined by RTQ-PCR and protein expression by Western blotting. Immunofluorescence microscopy and immunohistochemistry were also employed. Migration of CCA cells was assessed using modified Boyden chambers. Results: CXCR4 was clearly expressed in CCA cells of human CCA liver specimens. SDF-1 and hHSC conditioned medium (CM) promoted HuCCT-1 cell migration, which was abrogated by pre-incubation with AMD3100, a non-peptide antagonist of the CXCR4 receptor. In addition, HuCCT-1 cells silenced for CXCR4 did not migrate in presence of SDF-1. Both P-ERK and p-AKT were implicated in HuCCT-1 migration and showed a biphasic trend under stimulation of SDF-1. Finally, SDF-1 induced apoptotic rescue of HuCCT-1 cells by binding to CXCR4. Conclusions: Our study demonstrates that CCA cells migration and survival are modulated by the crosstalk between SDF-1, released by hHSC, and HuCCT-1 cells bearing CXCR4.
KW - Cholangiocarcinoma
KW - HuCCT-1 migration
KW - HuCCT-1 survival
KW - SDF-1/CXCR4 axis
UR - http://www.scopus.com/inward/record.url?scp=84866399814&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84866399814&partnerID=8YFLogxK
U2 - 10.1016/j.jhep.2012.06.012
DO - 10.1016/j.jhep.2012.06.012
M3 - Article
C2 - 22727731
AN - SCOPUS:84866399814
VL - 57
SP - 813
EP - 820
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 4
ER -