Sequence Motifs Specifying Homing and Metastasis to Bone
Abstract
We are using a novel approach developed at our Institute which makes use of random peptide libraries expressed on the surface of filamentous phage in order to identify in vivo peptides that may confer preferential homing properties to cancer cells for bone tissue. This approach is also complemented by in vitro panning using immortalized bone marrow stromal and endothelial cells as well as by expression cloning of cDNAs expressed differentially by metastatic breast cancer cells. To-date we have identified 10 peptides that appear to home to bone marrow by in vivo selection and one additional peptide that was positive in our in vitro selection system. Furthermore we have succeeded in immortalizing eleven different bone marrow cell lines which will be useful in our expression cloning experiments. These experimental approaches may lead to the identification of peptide sequences effective in blocking metastasis and serve as therapeutic compounds. This may lead to uncovering the basic mechanisms of bone metastasis by cancer cells which remains today one of the fundamental unresolved problems in tumor biology. Furthermore, identification of bone-specific homing sequences would enable the design of vectors to be used in gene therapy of genetic diseases affecting bone.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADA384097
Entities
People
- Jose L. Millan
Organizations
- Sanford Burnham Prebys Medical Discovery Institute