Sequence Motifs Specifying Homing and Metastasis to Bone
Abstract
Our aim is to identify molecules that mediate the specific homing of metastatic tumor cells to bone. Our approach involves the use of random peptide libraries expressed on the surface of filamentous phage as well as novel expression cloning strategies using immortalized bone marrow stromal and endothelial cells to detect the binding of COS-1 cells transfected with cDNAs from the bone metastatic MDA-MB-231 breast cancer cell line. Using both these approaches we have successfully identified 10 peptides by in vivo phage display and two novel cDNAs by expression cloning and work continues on the characterization of these molecules. This past year we also developed a new in vivo targeting strategy based on injecting transfected COS-1 cells into mice and recovering the transfected plasmids from those cells that home to the bone marrow. With this new strategy we have isolate 15 new promising clones. These experimental approaches will lead to the discovery of molecules involved in metastasis which remains today one of fundamental unresolved problems in tumor biology. Furthermore, identification of bone specific homing sequences could enable us to design vectors to be used in gene therapy of genetic diseases effecting bone and/or to block bone metastasis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA404682
Entities
People
- Jose L. Millan
Organizations
- Sanford Burnham Prebys Medical Discovery Institute