Gene Therapy for Osteolytic Breast Cancer Bone Metastasis
Annual rept. 1 Jun 2006-31 May 2007
ALABAMA UNIV IN BIRMINGHAM
Pagination or Media Count:
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. So far, 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 alpha 4-beta 1 integrin. Continuation of the ongoing studies in to next year will provide valuable information on therapeutic effects of this therapy for breast cancer bone metastasis.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research