Gene Therapy for Osteolytic Breast Cancer Bone Metastasis
Abstract
Bone is the frequent metastatic site for human breast cancer resulting in significant morbidity and mortality in patients with advanced disease. Osteoprotegerin (OPG) is a "decoy" receptor that competes with RANK for RANKL, thus, modulating the effects of RANKL. However, during the metastatic events involving cancer and stromal cell interaction, endogenous OPG levels are markedly reduced. Thus, OPG remains an effective molecule for future therapies for bone metastasis. We sought to achieve sustained effects of OPG combining cell therapy and gene therapy approaches. The aims were to determine therapeutic effects of stable OPG expression by rAAV gene therapy in a murine model of breast cancer bone metastasis, and to determine the synergistic effects of OPG gene therapy with bisphosphonate therapy in a murine model of breast cancer bone metastasis. Through this funding, we produced high-titer recombinant AAV vectors encoding osteoprotegerin, and tested the feasibility of MSC therapy for reducing osteolysis in bone initiated by cancer growth. Also we established a method for bone homing of ex vivo cultured MSC by transient expression of alpha4beta1 integrin.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2009
- Accession Number
- ADA516575
Entities
People
- Selvarangan Ponnazhagan
Organizations
- University of Alabama