Modulating the interaction of CXCR4 and CXCL12 by low-molecular-weight heparin inhibits hepatic metastasis of colon cancer

Ma, Lixin, Qiao, Haiquan, He, Changjun, Yang, Qian, Cheung, Chun Hei Antonio, Kanwar, Jagat R. and Sun, Xueying 2012, Modulating the interaction of CXCR4 and CXCL12 by low-molecular-weight heparin inhibits hepatic metastasis of colon cancer, Investigational new drugs, vol. 30, no. 2, pp. 508-517, doi: 10.1007/s10637-010-9578-0.

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Title Modulating the interaction of CXCR4 and CXCL12 by low-molecular-weight heparin inhibits hepatic metastasis of colon cancer
Author(s) Ma, Lixin
Qiao, Haiquan
He, Changjun
Yang, Qian
Cheung, Chun Hei Antonio
Kanwar, Jagat R.ORCID iD for Kanwar, Jagat R.
Sun, Xueying
Journal name Investigational new drugs
Volume number 30
Issue number 2
Start page 508
End page 517
Total pages 10
Publisher Springer New York LLC
Place of publication New York, N.Y.
Publication date 2012-04
ISSN 0167-6997
Keyword(s) colon cancer
liver metastasis
low-molecular-weight heparin
stromal cell-derived factor 1α
HCT-116 cells
Summary Liver metastasis is the major obstacle for prolonging the survival of colon cancer patients. Low-molecular-weight heparin (LMWH), a common drug for venous thromboembolism, has displayed beneficial effects in improving the survival of cancer patients, though the mechanism remains unclear. This study aimed to investigate the effects of LMWH on hepatic metastasis of colon cancer and its underlying molecular mechanism by targeting the interaction of the chemokine receptor CXCR4 and its ligand CXCL12 (formerly known as stromal cell-derived factor 1α, SDF-1α), as the CXCR4-CXCL12 axis has been shown to regulate the interaction of cancer cells and stroma. Experimental results revealed that LMWH (Enoxaparin, 3500-5500 Da) inhibited the CXCL12-stimulated proliferation, adhesion and colony formation of human colon cancer HCT-116 cells that highly expressed CXCR4. Interestingly, LMWH or an anti-CXCR4 blocking antibody diminished the migrating and invading abilities of HCT116 cells stimulated by the recombinant CXCL12 protein or liver homogenates which contained endogenous CXCL12 protein. Although LMWH did not significantly inhibit the growth of subcutaneous colon tumors, it significantly suppressed the formation of hepatic metastasis established by intrasplenic injection of colon cancer cells in nude Balb/c mice and also downregulated the expression of CXCL12 in hepatic sinusoidal endothelial cells. The results suggest that LMWH inhibits the formation of hepatic metastasis of colon cancer by disrupting the interaction of CXCR4 and CXCL12, supporting that perioperative administration of LMWH may help to prevent the seeding and subsequent growth of hepatic metastases of colon cancer cells.
Language eng
DOI 10.1007/s10637-010-9578-0
Field of Research 060199 Biochemistry and Cell Biology not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1 Refereed article in a scholarly journal
HERDC collection year 2010
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