Expression of CXC chemokine receptors 1-5 and their ligands in human glioma tissues: Role of CXCR4 and SDF1 in glioma cell proliferation and migration.Bajetto A, Barbieri F, Dorcaratto A, Barbero S, Daga A, Porcile C, Ravetti JL, Zona G, Spaziante R, Corte G, Schettini G, Florio T.
Department of Oncology, Biology and Genetics, University of Genova, Viale Benedetto XV, 2, 16132 Genova, Italy.
Chemokines have been involved in cellular processes associated to malignant transformation such as proliferation, migration and angiogenesis.
The expression of five CXC chemokine receptors and their main ligands was analysed by RT-PCR in 31 human astrocytic neoplasms. The mRNAs for all the receptors analysed were identified in a high percentage of tumours, while their ligands showed lower expression.
CXCR4 and SDF1 were the most frequently mRNA identified (29/31 and 13/31 of the gliomas studied, respectively). Thus, we further analysed the cell localization of CXCR4 and SDF1 in immunohistochemistry experiments.
We show a marked co-localization of CXCR4 and SDF1 in tumour cells, mainly evident in psudolpalisade and microcystic degeneration areas and in the vascular endothelium.
In addition, hSDF1alpha induced a significant increase of DNA synthesis in primary human glioblastoma cell cultures and chemotaxis in a glioblastoma cell line.
These results provide evidence of the expression of multiple CXC chemokines and their receptors in brain tumours and that in particular CXCR4 and SDF1 sustain proliferation and migration of glioma cells to promote malignant progression.
PMID: 16621164 [PubMed - in process]
ncbi.nlm.nih.gov
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Northwest Biotherapeutics to Present Data on CXCR4 at the Cambridge Healthtech Institute's Targeted Cancer Therapies Conference
CXCR4 Target Plays Central Role in Cancer Progression in More Than 75% of Cancers
BOTHELL, Wash., Aug. 17 /PRNewswire-FirstCall/ -- Northwest Biotherapeutics (OTC: NWBT.OB) (BULLETIN BOARD: NWBT.OB) today announced that the company will be presenting preclinical data on a monoclonal antibody to CXCR4 at the Cambridge Healthtech Institute's 2nd Annual Targeted Cancer Therapies Conference, August 21st-22nd at the Royal Sonesta Hotel in Cambridge, Massachusetts. CXCR4 is one of the most important cancer targets discovered in recent years, because it plays a central role in all three stages of cancer progression, and because it does so in over 75% of all cancers. Company President Alton Boynton, Ph.D., will give an oral presentation during the New Targets session at the CHI conference on Monday, August 21st at 4:30 PM EDT. Dr. Boynton will be available to discuss the findings and the planned development of CXCR4 as a highly promising new cancer therapy target.
CXCR4 is over-expressed in greater than 75% of cancers, including breast, ovarian, lung, colon, prostate, kidney, melanoma, brain, esophageal, and pancreatic -- as well as numerous forms of leukemia, and childhood cancers such as acute lymphocytic leukemia and neuroblastoma. Northwest Biotherapeutics previously completed and reported on several preclinical studies using monoclonal antibodies to block CXCR4 receptor function, and reported significant inhibition of cancer cell proliferation, motility and invasion in multiple preclinical models both in vitro and in vivo.
It is well documented and accepted that CXCR4 plays an important role in all three fundamental aspects of cancer: (1) proliferation of the primary tumor, (2) migration of tumor cells away from the primary tumor, and (3) invasion and establishment of metastases at distant sites such as bone, lung and brain. "The fact that CXCR4 plays a role in three functional aspects of cancer is rare, and therapeutically offers significant advantages for an antibody based therapy," stated Dr. Alton Boynton. "CXCR4 offers an exceptional therapeutic opportunity to prevent proliferation of primary tumors and to prevent the metastatic spread of the disease."
In March 2005, Northwest Biotherapeutics announced that it was issued a United States patent covering the broad use of CXCR4 antibodies for cancer therapeutics.
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