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Bone Marrow Suppression by c-Kit Blockade Enhances Tumor Growth of Colorectal Metastases through the Action of Stromal Cell-Derived Factor-1
Joint Authors
Kollmar, Otto
Rupertus, Kathrin
Schilling, Martin K.
Haberl, Gudrun C. Y.
Scheuer, Claudia
Menger, Michael D.
Source
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2011-10-02
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
Background.
Mobilization of c-Kit+ hematopoietic cells (HCs) contributes to tumor vascularization.
Whereas survival and proliferation of HCs are regulated by binding of the stem cell factor to its receptor c-Kit, migration of HCs is directed by stromal cell-derived factor (SDF)-1.
Therefore, targeting migration of HCs provides a promising new strategy of anti-tumor therapy.
Methods.
BALB/c mice (n=16) were pretreated with an anti-c-Kit antibody followed by implantation of CT26.WT-GFP colorectal cancer cells into dorsal skinfold chambers.
Animals (n=8) additionally received a neutralizing anti-SDF-1 antibody.
Animals (n=8) treated with a control antibody served as controls.
Investigations were performed using intravital fluorescence microscopy, immunohistochemistry, flow cytometry and western blot analysis.
Results.
Blockade of c-Kit significantly enhanced tumor cell engraftment compared to controls due to stimulation of tumor cell proliferation and invasion without markedly affecting tumor vascularization.
C-Kit blockade significantly increased VEGF and CXCR4 expression within the growing tumors.
Neutralization of SDF-1 completely antagonized this anti-c-Kit-associated tumor growth by suppression of tumor neovascularization, inhibition of tumor cell proliferation and reduction of muscular infiltration.
Conclusion.
Our study indicates that bone marrow suppression via anti-c-Kit pretreatment enhances tumor cell engraftment of colorectal metastases due to interaction with the SDF-1/CXCR4 pathway which is involved in HC-mediated tumor angiogenesis.
American Psychological Association (APA)
Rupertus, Kathrin& Haberl, Gudrun C. Y.& Scheuer, Claudia& Menger, Michael D.& Schilling, Martin K.& Kollmar, Otto. 2011. Bone Marrow Suppression by c-Kit Blockade Enhances Tumor Growth of Colorectal Metastases through the Action of Stromal Cell-Derived Factor-1. Journal of Oncology،Vol. 2012, no. 2012, pp.1-12.
https://search.emarefa.net/detail/BIM-453748
Modern Language Association (MLA)
Rupertus, Kathrin…[et al.]. Bone Marrow Suppression by c-Kit Blockade Enhances Tumor Growth of Colorectal Metastases through the Action of Stromal Cell-Derived Factor-1. Journal of Oncology No. 2012 (2012), pp.1-12.
https://search.emarefa.net/detail/BIM-453748
American Medical Association (AMA)
Rupertus, Kathrin& Haberl, Gudrun C. Y.& Scheuer, Claudia& Menger, Michael D.& Schilling, Martin K.& Kollmar, Otto. Bone Marrow Suppression by c-Kit Blockade Enhances Tumor Growth of Colorectal Metastases through the Action of Stromal Cell-Derived Factor-1. Journal of Oncology. 2011. Vol. 2012, no. 2012, pp.1-12.
https://search.emarefa.net/detail/BIM-453748
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-453748