Untangling the Matrix in Medulloblastoma
Medulloblastoma is the most common malignant brain tumor in childhood. While many children are cured with current therapies, over 1/3 still die from their cancer and many survivors suffer lifelong disability. With continued research into novel therapies, there is hope that more children will survive this disease with fewer long-term side effects. Traditionally, research has focused on the cancer cells themselves and the pathways that are important for tumor growth and spread. In medulloblastoma, there is much less known about the role of the molecules that make up the scaffolding that surrounds the cells, the so-called extracellular matrix (ECM). The nature of the ECM varies greatly between different organs in the body and is often altered in malignancy. In many other cancers, this matrix plays important roles in cell survival and invasion. It is also very important in normal brain development.
Preliminary results indicate that the matrix in many medulloblastoma tumors is very different from that of normal brain and that the tumor cells themselves actively contribute to the ECM. This raises the possibility that targeting the matrix in medulloblastoma may damage tumor cells, but not normal nervous tissue, which may lead to the development of less neurotoxic therapies.
This proposal outlines experiments to determine the exact nature of the ECM in medulloblastoma, the effect of the ECM on tumor cell growth and migration, and the pathways involved in these processes.