These cell lines (based on the widely used B16 murine melanoma cell line) were transduced with retroviral vectors encoding cDNA for either CXCR4 or CCR10 under control of a TET-dependent promoter.

The chemokine receptor CXCR4 functions in normal cells, but has been shown to be the most common chemokine receptor expressed on cancer cells, including melanoma, colon, breast, and lung cancers. It plays roles in angiogenesis and cancer cell survival as well as metastasis. CCR10 has also been shown to be expressed by melanoma cells. Like CXCR4, expression of CCR10 can enhance cancer cell survival and block immune recognition of cancer cells. Antagonists of CXCR4 and CCR10, under various conditions, have decreased metastasis or prevented tumor formation after implantation of cancer cells in mice.

 

These cell lines are based on the widely used B16 murine melanoma cell line.  The cell lines were transduced with retroviral vectors encoding cDNA for either CXCR4 or CCR10 under control of a TET-dependent promoter. Both lines achieve greater than 10 fold induction of the respective genes (proteins), which has been confirmed by surface antibody staining using flow cytometry. These cell lines are ideally suited for studying the effect of these chemokine receptors in tumor growth or metastasis. They are also useful for developing a mouse model for studying the effect of down-regulating these receptors specifically in melanoma cells. This would mimic the effect of antagonists without the confounding effects of systemically inhibiting CXCR4 or CCR10. By either adding or removing dietary administered doxycycline, receptor expression can be regulated to assess the role of these two receptors in a variety of cancer-related assays.

 

Applications: 

• Study the effect of chemokine receptors in tumor growth or metastasis
• Test CXCR4 and CCR10 antagonists in preclinical studies
• Develop B16 melanoma mouse model mimicking the effect of chemokine receptor antagonists

 

Advantages: 

• Ability to regulate in vitro and in vivo expression of the chemokine receptor
• Ability to investigate the in vivo role in cancer cells of doxycycline control of chemokine receptor expression

 

Development Status: 

The technology is currently in the preclinical stage of development.

 

Publication: 

T Kakinuma, ST Hwang. Chemokines, chemokine receptors, and cancer metastasis. J Leukoc Biol. 2006 Apr;79(4):639-651.  [PubMed abs]

 

 

Preclinical

HHS Reference No. E-345-2008/0 -- Research Material.  Patent protection is not being sought for either technology.

 

Inventor: 

Sam T. Hwang (NCI)

 

Licensees Sought: 

Available for non-exclusive licensing under a Biological Materials License Agreement.