Doxycycline-Inducible B16 Melanoma Cell Lines Expressing CXCR4 or CCR10
Description of Invention:
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.
Market:
Cancer is the second leading cause of death in the U.S. and it is estimated that more than 1 million Americans develop cancer in a year.
Patent Status:
DHHS Reference No. E-345-2008/0 -- Research Material
Patent protection is not being sought for either technology.
Relevant Publication: T Kakinuma, ST Hwang. Chemokines, chemokine receptors, and cancer metastasis. J Leukoc Biol. 2006 Apr;79(4):639-651. [PubMed abs]
Licensing Status: Available for non-exclusive licensing under a Biological Materials License Agreement.
Portfolios: Cancer
Cancer -Research Materials-Other Cancer -Research Materials
For Additional Information Please Contact: Adaku Nwachukwu J.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: 301 435-5560
Email: madua@mail.nih.gov
Fax: 301 402-0220
