Modulation of Angiogenesis and Immune Response in Canine Osteosarcoma by BMP-2 and Mesenchymal Stem Cells

Abstract

Osteosarcoma is the most frequent bone tumor that predominantly targets the adolescent aged between 10- 25 years. In the veterinary oncology, osteosarcoma accounts 80-95% of the bone tumors diagnosed in dogs. Humans and dogs share several similarities in regard to the physiological and molecular aspects of osteosarcoma development. For this reason dogs have been used as a homologous model to human, which have been showed promising in vitro results. Herein, from implanted tumor in nude mice we analyzed the effects of a combination of stem cells from canine bone marrow and bone morphogenetic protein (BMP-2) on the treatment of osteosarcoma. The results showed that this combination changed the expression of markers of cell death, leading to an increase of caspase 3 expression, and decreased of Bcl-2 expression, as well as decreased in cell proliferation (Ki-67 and p53) and receptor of angiogenesis pathways (CD34, COX-2, IL-6, IL-8, and VEGF). The tumor environment was modified by decreased expression of CD4 + CD25 + resulting in increased CD8 + cytotoxic. In conclusion, these data showed that the treatment using the combination of stem cells from canine bone marrow and bone morphogenetic protein (BMP-2) emerges as a potential therapeutic tool for the osteosarcoma treatment.