Sequence Motifs Specifying Homing and Metastasis to Bone
Abstract
Our overall aim is to identify peptide motifs or molecules that may mediate the specific homing of metastatic tumor cells to bone. Our approaches involves the use of random peptide libraries expressed on the surface of filamentous phage as well as an expression cloning strategy using immortalized bone marrow stromal and endothelial cells to detect the binding of Cos-1 cells transfected with complementary DNAs from the bone metastatic MDA-MB-23 1 breast cancer cell line. Using both these approaches we have successfully identified 10 peptides by in vivo phage display and two novel complementary DNAs (A3 and A5) by expression cloning and work continues on the characterization of these molecules. In particular by Northern blot analysis the A3 messenger RNA is expressed in high amount in bone metastatic tumor cell lines, while A5 appears to be overexpressed in breast and prostate cancer cell lines irrespective of their metastatic potential. These experimental approaches will lead to the discovery of molecules that may help us uncover the basis mechanisms of bone metastasis by cancer cells 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, 2000
- Accession Number
- ADA389727
Entities
People
- Jose Luis Millan
Organizations
- Sanford Burnham Prebys Medical Discovery Institute