Inhibition of CXCR4 activity with AMD3100 decreases invasion of human colorectal cancer cells in vitro

Abstract

Inhibition of CXCR4 activity with AMD3100 decreases invasion of human colorectal cancer cells in vitro. World J Gastroenterol 2008; 14(15): 2308-2313 Available from: URL: http://www.wjgnet. com/1007-9327/14/2308.asp DOI: http://dx.doi.org/10.3748/ wjg.14.2308 INTRODUCTIONStromal cell-derived factor-1 (SDF-1 or CXCL12) and its unique receptor CXC chemokine receptor-4 (CXCR4) have prominent roles in invasion and metastasis of a diverse number of cancers. The interaction between SDF-1 and CXCR4 has been shown to direct tumor cells to organ sites with high levels of SDF-1 expression, which suggests this molecular pair plays a key role in chemotaxis and homing of metastatic cells. Convincing evidence indicates elevated CXCR4 expression in primary tumors is associated with lymph node metastasis in breasts [1][2][3][4] , head and neck [5] , and colon [6] . Furthermore, CXCR4 expression is associated with intraperitoneal carcinomatosis of ovarian [7] and gastric [8] cancer. High or persistent expression of CXCR4 has been associated with poor prognosis in osteosarcoma [9] , epithelial ovarian cancer [10] , colon cancer [6,11,12] , esophageal carcinoma [13] , and melanoma [14] . Recently, intensive research has shown that binding of CXCL12 to CXCR4 plays a role in tumor angiogenesis by influencing the secretion of vascular endothelial growth factor (VEGF) [15] and increasing invasion associated with matrix metalloproteinase (MMP)-9 activation [16] . Therefore, interruption of the interaction between CXCR4 and SDF-1 has received considerable attention since it may provide a means of inhibiting the metastatic process. AMD3100, a bicyclam molecule, has been identified as a specific inhibitor of CXCR4. It had originally been developed as an inhibitor of T-tropic human Abstract AIM: To investigate the effect and mechanism of blockade of the CXC chemokine receptor-4 (CXCR4) signaling pathway by AMD3100, a small non-peptide CXCR4 inhibitor, on invasion and metastasis of colorectal cancer cells in vitro .

CXCL12-CXCR4 Promotes Proliferation and Invasion of Pancreatic Cancer Cells

“…The proliferation rate and growth patterns of tumors have significant impacts on disease development and prognosis of the patients; indeed, the proliferation rate of tumor cells can indirectly reflect the tumor malignancy (Ravi et al, 1998). Proliferation of malignant cells can be affected by changes in many different proteins, but evidence indicates that the CXCL12-CXCR4 biological axis is important to this process (Chen et al, 2006;Li et al, 2008). We found that, in fact, the proliferation rate of pancreatic cancer cells was significantly increased in the presence of exogenous CXCL12.…”

The AMD3100 story: The path to the discovery of a stem cell mobilizer (Mozobil)

“…AMD3100 has also been reported to decrease invasion of human colorectal cancer cells in vitro [46]. Thus, blocking the interaction of CXCR4 with SDF-1 (CXCL12) may provide a novel means of preventing the invasion and metastasis of colorectal cancer.…”

Expression of CXCR-4 and IDO in human colorectal cancer: An immunohistochemical approach

“…CXCR4 has been considered as a potential therapeutic target in several studies. A number of in vitro studies have reported that inhibiting the interactions of chemokine CXCR4 using antibodies or small molecules markedly reduces the metastasis of colorectal cancer cells (30,31); this approach could become a promising therapy for colon cancer.…”