Abstract
Background: Whereas the chemokine stromal cell-derived factor (SDF)-1 and its receptor CXCR4 are known to be involved in the metastatic process of colorectal cancer, their role in regulating angiogenesis and tumor growth during liver regeneration is unknown. Using an established murine model of colon cancer metastasis, we analyzed the potential of liver resection associated-SDF-1 to promote angiogenesis and tumor growth of colorectal metastases. Methods: 70 % hepatectomized BALB/c mice were treated with an anti-SDF-1 or control-antibody and remnant livers were analyzed for the regenerative process during a 7d observation period. Secondarily, after a 30 % hepatectomy, GFP-transfected CT26. WT colorectal cancer cells were implanted into dorsal skinfold chambers of syngeneic BALB/c mice. Animals were treated with an anti-SDF-1 or control-antibody starting at different time points after tumor cell implantation. Tumor vascularization and growth, proliferation, apoptosis, CXCR4 and VEGF expression were studied over 14 days using intravital fluorescence microscopy, histology, immunohistochemistry and western blot analyses. Results: Functional inhibition of SDF-1 did not inhibit regeneration of the remnant liver after major hepatectomy. Anti-SDF-1 treatment delayed tumor cell engraftment but not growth of established metastases. The initial delay of engraftment was associated with a compensatory stimulation of angiogenesis and leakage of the tumor vessels compared to controls. Furthermore, anti-SDF-1 treatment was associated with a significant induction of CXCR4 and VEGF expression in the tumors. Tumor cell apoptosis was increased only during the early phase of liver regeneration. Conclusion: Our study indicates that neutralization of SDF-1 does not inhibit regeneration of the remnant liver after hepatectomy and does not decrease extrahepatic tumor growth due to an accelerated angiogenesis via a CXCR4/VEGF-dependent pathway.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Literatur
Kollmar O, Rupertus K, Scheuer C et al. (2007) Stromal cell-derived factor-1 promotes cell migration and tumor growth of colorectal metastasis. Neoplasia 9: 862–870
Mavier P, Martin N, Couchie D et al. (2004) Expression of stromal cell-derived factor-1 and of its receptor CXCR4 in liver regeneration from oval cells in rat. Am J Pathol 165: 1969–1977
Harun N, Nikfarjam M, Muralidharan V et al. (2007) Liver regeneration stimulates tumor metastases. J Surg Res 138:284–290
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2008 Springer Medizin Verlag Heidelberg
About this paper
Cite this paper
Rupertus, K. et al. (2008). Die Blockade von SDF-1 nach Leberresektion hat aufgrund eines zusätzlich aktivierten CXCR4/VEGF-abhängigen Signalwegs keinen Einfluss auf das metastatische Tumorwachstum. In: Arbogast, R., Schackert, H.K., Bauer, H. (eds) Chirurgisches Forum 2008. Deutsche Gesellschaft für Chirurgie, vol 37. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-78833-1_19
Download citation
DOI: https://doi.org/10.1007/978-3-540-78833-1_19
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-78821-8
Online ISBN: 978-3-540-78833-1
eBook Packages: Medicine (German Language)