The TGF-Beta Pathway: A Potential Mediator of Medulloblastoma Progression
Donya Aref, Connor Moffatt, Arie Perry, Sameer Agnihotri, Sidney E Croul. University of Toronto, Toronto, ON, Canada; University of California San Francisco, San Francisco, CA
Background: Medulloblastoma, an embryonal neuroepithelial tumour arising in the cerebellum, is the most common malignant brain tumor of childhood. Although current treatment regimens have significantly improved survival over the past decades, recurrent and/or metastatic medulloblastoma still spells poor prognosis for patients. Aggressiveness is marked by increased growth and decreased responsiveness to available therapies. However the molecular changes that underlie these pathophysiological behaviors during medulloblastoma progression are not well understood.
Design: To further identify pathways of signaling that contribute to medulloblastoma metastasis and recurrence we decided to undertake an unbiased, whole genome expression study. We performed microarray experiments, using human patient matched primary and recurrent or metastatic samples. This was supplemented with microarray data derived from murine samples from two different mouse models of medulloblastoma, the Ptch+/- and Smo/Smo models, that present with differing clinical histories and disease aggressiveness.
Results: At both the human and murine levels we identified the Transforming Growth Factor-Beta (TGF-Beta) as a potential contributor to medulloblastoma progression/metastasis. Smad3, a major downstream component of the TGF-Beta pathway, was also evaluated using immunohistochemistry in both developing and malignant human and murine tissue and was shown to correlate with disease progression. Currently we are in the process of assessing the contribution of this signaling pathway in an in vitro setting.
Conclusions: This work identifies TGF-Beta as a potential contributor to medulloblastoma progression and metastasis both at the level of RNA and protein expression in the human and murine species. To our knowledge, this is the first study that implicates TGF-Beta as a contributor to medulloblastoma progression and metastasis.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 262, Tuesday Afternoon