CD36-Sphingosine 1-Phosphate Axis in Osteosarcoma Progression
Bone is usually the site for metastasis of different cancers such as breast and prostate. However, osteosarcoma (OS) is primarily a bone cancer that starts in bone. Most OS occur in children and teens in areas where bone is growing rapidly such as ends of long bone. OS is the eighth most common form of childhood cancer and approximately 35% of all primary bone cancers and can lead to a life-long debilitating state for patients, thus it is important to study this cancer so that novel treatment modalities can be developed. In recent years importance of tumor surroundings/microenvironment has emerged. A potentially exciting strategy for arresting tumors is based on the fact that tumor metastasis is dependent on ability of tumor to establish a supportive microenvironment in the host. OS microenvironment consists of cells such as fibroblasts and osteoblasts. Osteoblasts are generally thought to arise from mesenchymal cells in bone marrow. Our studies have shown that the other stem cell in bone marrow, hematopoietic stem cells (HSC), can also give rise to osteoblasts (H-Obs). Understanding the role of H-Obs in OS microenvironment can help identify factors that aid in metastasis of OS.
Project Goal: In this grant, we will be examining the role of lipid sensor, CD36 and sphingolipid pathway in OS progression by the non-malignant H-Obs in tumor stoma. Results obtained can help us identify the specific target molecules to arrest OS progression. Thus, these studies are significant as the findings can be translated to clinics as a therapy in future.
Project Update 2022: Our data confirms that CD36 and S1P are indeed involved in the progression of osteosarcoma both in mice as well as human cells, thus making these studies translatable. We are currently working on examining that the inhibition of which molecule or their combination can bring about the maximum arrest in the progression of osteosarcoma, in pre-clinical mice studies using mice and human cells. Studies show that the five-year survival rate for the localized tumor is 77% but this drops drastically to only 27% if the tumor spreads to the lungs. The major treatments for this cancer are radiation therapy, chemotherapy and surgery including amputation. Thus, osteosarcoma can lead to a life-long debilitating state for the patients. Hence, it is very important to study this cancer and develop novel treatment modalities in order to keep it localized and prevent its spread. This will increase the five-year survival rate and improve the quality of life. As some of our pre-clinical studies in mice show that inhibitors of CD36 and S1P can arrest the progression of osteosarcoma and increase the survival rate, this would be a major advance in the field of osteosarcoma research and can be pursued further for clinical studies in the future.
