Medulloblastoma (MB) is the most common malignant brain tumor in children. Despite aggressive tumor treatment, a significant proportion of MB patients still succumbs to this devastating disease. Improved strategies to treat MB can only come from deeper understandings of molecular and cellular basis for MB tumorigenesis.
Our research at Fox Chase Cancer Center has been focused on hedgehog pathway associated MB, which accounts for approximately 30% of human MB cases. 15-20% of mice with deficiency in Patched-1 gene (Ptch1, an antagonizing receptor of hedgehog pathway) develop MB at around 30 weeks of age. We previously demonstrated that astrocytes, a major component of MB microenvironment, play a critical role in MB progression in ptch1 deficient mice. Recently we found that MB cells activated astrocytes in their microenvironment, and stimulated astrocytes to secrete multiple growth factors for tumor growth. Based on these observations, we hypothesize that mutual interactions between astrocytes and tumor cells are necessary for MB growth.
What are the goals of this project?
The goals of this project are to examine the mutual support of astrocytes and tumor cells purified from human MB, by a co-culture method or intracranial transplantation and to investigate the alterations of gene/protein expression in tumor cells and astrocytes after being co-cultured or cultured alone by RNA sequencing or MS-Spec.
What is the impact of this project?
The findings from this project will shed light on the important functions of tumor microenvironment in MB tumorigenesis and also demonstrate tumor microenvironment as a promising therapeutic target for MB treatment.
Why the CBTN request is important to this project?
We have been always using primary MB cells isolated from Ptch1 deficient mice. We wish to be able to validate our research findings in human MB, which will pave the road to rapidly translate our findings to clinics. Currently we do not have any MB samples from human patients.
The Children's Brain Tumor Tissue Consortium contributed to this project by providing tissue for cell line generation.
Medulloblastomas comprise the vast majority of pediatric embryonal tumors and by definition arise in the posterior fossa, where they constitute approximately 40% of all posterior fossa tumors. Other forms of embryonal tumors each make up 2% or less of all childhood brain tumors.The clinica