Fibroblast activation protein is a potential therapeutic target in myeloma

06-13-2006

Fibroblast activation protein is a potential therapeutic target in myeloma.

According to a study from the United States, "The microenvironment plays a critical role in facilitating cancer progression and metastasis. We previously demonstrated the ability of osteoclasts to support primary myeloma plasma cell (MM PC) growth."

"Our study on the role of the bone marrow (BM) microenvironment in myeloma, using global gene expression profiling, has identified fibroblast activation protein (FAP) as one of 28 genes significantly overexpressed in cocultured osteoclasts."

"Because FAP has been previously implicated in tumorigenesis and shown to be selectively expressed by the reactive stroma of epithelial tumors," wrote Y. Ge and colleagues at the University of Arkansas for Medical Sciences, "we focused our study on the role of this serine protease in myeloma."

"Using quantitative polymerase chain reaction amplification, we demonstrated upregulation of FAP by cocultured osteoclasts and mesenchymal stem cells, and in whole myelomatous human bone in SCID-hu mice," investigators reported.

Ge continued, "Immunohistochemical analysis of myelomatous bone sections revealed FAP expression by osteoclasts, osteogenic cells, fibrotic stroma and certain adipocytes and vascular endothelial cells. FAP was not expressed in PCs by all these methods. Inhibition of FAP expression with the use of small-interference RNA reduced MM PC survival in cocultures."

"Our results indicate that FAP is critical for the interaction of MM cells with the BM microenvironment; a potential therapeutic target in myeloma," concluded scientists.

Ge and colleagues published their study in British Journal of Haematology (Fibroblast activation protein (FAP) is upregulated in myelomatous bone and supports myeloma cell survival. Br J Haematol, 2006;133(1):83-92).

For more information, contact S. Yaccoby, University of Arkansas Med Science, Myeloma Institute Research & Therapy, 4301 W Markham, Slot 776, Little Rock, AR 72205, USA.

Publisher contact information for the British Journal of Haematology is: Blackwell Publishing, 9600 Garsington Rd., Oxford OX4 2DQ, Oxon, England.

Keywords: Little Rock, Arkansas, United States, Multiple Myeloma, Fibroblast Activation Protein, Mesenchymal Stem Cells, Therapeutic Target, Bone Marrow Microenvironment.

This article was prepared by Cancer Gene Therapy Week editors from staff and other reports. Copyright 2006, Cancer Gene Therapy Week via NewsRx.com.