The CXCR4 Receptor, Solid Cancer Metastasis and Quercetin

In May of 2005, I wrote a Blog about CXCR4 and its role in cancer metastasis and HIV induced death. Tannic acid was the only molecule that I could find that inhibited the expression of this critically important membrane receptor molecule.

http://grouppekurosawa.com/blog/2005/05/holy-grail-for-cancer-and-hiv.htm

Well, that was then and this is now, a new year.

CXCR4 is present on almost all cancer and leukemia cells and it promotes their metastasis or movement throughout the body. For HIV, when the HIV virus mutates, the membrane gp120 protein binds CXCR4 and promotes cellular the fusion of infected and non-infected CD4 T cells. The development of CXCR4 "loving" strains of virus and the decline of CD4 T cells is often considered the beginning of the clinical syndrome we call AIDS.

Some new background information follows.

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=pubmed&
dopt=Abstract&list_uids=16368946&itool=pubmed_docsum

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=pubmed&
dopt=Abstract&list_uids=16132577&itool=pubmed_docsum

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=pubmed&
dopt=Abstract&list_uids=15486895&itool=pubmed_docsum

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=pubmed&
dopt=Abstract&list_uids=15647826&itool=pubmed_docsum

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=pubmed&
dopt=Abstract&list_uids=15180966&itool=pubmed_docsum

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=pubmed&
dopt=Abstract&list_uids=15180966&itool=pubmed_docsum

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=pubmed&
dopt=Abstract&list_uids=15548713&itool=pubmed_docsum

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=pubmed&
dopt=Abstract&list_uids=16230077&itool=pubmed_docsum

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=pubmed&
dopt=Abstract&list_uids=12839981&itool=pubmed_docsum

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=pubmed&
dopt=Abstract&list_uids=16000558&itool=pubmed_docsum

The CXCR4 receptor, when over expressed on cancer and leukemia cells, promotes BOTH their survival and migration throughout the body. We have NEVER had a viable inhibitor of CXCR4 over expression. Until now...

Please take time to read the abstracts referenced above. The over expression of CXCR4 is common for ALL cancers and leukemias. Also keep in mind that the metastasis of cancer cells into the bone marrow is one of the worst things that can happen to someone with cancer. Killing cancer cells in the bone marrow is very difficult. Bone Mets, as it is called, is also horribly painful.

In this paper, epidermal growth factor, a protein hormone that promotes the growth of many cancers, is shown to over express CXCR4 on lung cancer cells. EGF activates the PI-3K/AKT/mTOR pathway. The term "mammalian target of rapamycin" means mTOR.

http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=pubmed&
dopt=Abstract&list_uids=15802268&itool=pubmed_docsum

As discussed previously, quercetin will block this biochemical pathway. This means that quercetin is also a blocker of CXCR4 expression, among its many other roles. And it can do so in concentrations that can be attained in the body.

This is very good news. In the next Blog, I will discuss the role of CXCR4 in the development of different leukemias.

Stay tuned...it's going to be a good year.

Grouppe Kurosawa, Medicine in the Public Interest
(http://www.grouppekurosawa.com)