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Hepatic ischemia-reperfusion increases circulating bone marrow-derived progenitor cells and tumor growth in a mouse model of colorectal liver metastases.
- Source :
-
The Journal of surgical research [J Surg Res] 2013 Oct; Vol. 184 (2), pp. 888-97. Date of Electronic Publication: 2013 May 21. - Publication Year :
- 2013
-
Abstract
- Background: Hepatic pedicle clamping is often required to reduce blood loss and transfusion during liver resection. However, the question remains whether use of hepatic pedicle clamping promotes tumor growth. Endothelial progenitor cells (EPCs) are mobilized from bone marrow in response to tissue ischemia, which allows neovascularization of ischemic tissue. It has been suggested that EPCs are involved in tumor progression. We hypothesized that hepatic ischemia reperfusion (I/R)-induced mobilization of EPCs could enhance growth of microscopic tumor, therefore promoting liver metastasis in a mouse model of colorectal cancer.<br />Materials and Methods: We used mouse models of hepatic I/R and hind limb ischemia. For comparison, we studied mice that underwent limb ischemia as positive controls of EPC mobilization. At day 0, we divided 40 mice into four groups: hepatic I/R, hind limb ischemia, combined hepatic I/R and hind limb ischemia, and control (sham midline incision laparotomy). At day 2, we induced liver metastasis in all mice by injecting CT-26 cells into the spleen. Time-dependent circulating EPCs were determined by flow cytometry. We evaluated liver metastasis and microvascular density on day 21.<br />Results: The number of circulating progenitor cells increased rapidly in the ischemic groups compared with the control group. Hepatic I/R significantly increased tumor outgrowth compared with the control group. Increased tumor growth was associated with enhanced CD31-positive microvascular density in liver tissue.<br />Conclusions: Hepatic I/R leads to mobilization of bone marrow-derived EPCs and enhanced intra-hepatic angiogenesis, which is associated with increased tumor burden in an animal model of colorectal liver metastasis.<br /> (Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Cell Count
Cell Line, Tumor
Chemokine CXCL12 blood
Disease Models, Animal
Disease Progression
Female
Liver Neoplasms pathology
Mice
Mice, Inbred BALB C
Neoplasm Metastasis physiopathology
Neovascularization, Pathologic physiopathology
Bone Marrow Cells pathology
Cell Proliferation
Colorectal Neoplasms pathology
Hematopoietic Stem Cells pathology
Liver blood supply
Liver Neoplasms secondary
Reperfusion Injury physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1095-8673
- Volume :
- 184
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Journal of surgical research
- Publication Type :
- Academic Journal
- Accession number :
- 23726239
- Full Text :
- https://doi.org/10.1016/j.jss.2013.04.069