Seeding of medulloblastoma is the most influential prognostic factor for survival, but little has been known about the molecular mechanism of seeding in medulloblastoma. Inhibitor of differentiation (ID) genes are implicated as promoter of tumor progression and metastasis in many human cancers. We investigated the expression and functional roles of ID genes in terms of seeding and prognosis of medulloblastoma. Significantly higher ID3 expression was observed in medulloblastoma with seeding than in tumors without seeding. In vitro studies using D283 medulloblastoma cells and ID3-siRNA showed that ID3 knockdown resulted in decreased proliferation, enhanced apoptosis, and suppressed migration. We made a seeding model of medulloblastoma in mice and injected a stable cell line with ID3 knockdown with shRNA. ID3 knockdown in vivo inhibited growth of primary tumor and development of leptomeningeal seeding and prolonged survival of animals compared with controls. A mRNA mini-array revealed that ID3 knockdown leads to up-regulation (TIMP3, ITGB4, COL12A1, ADAMTS8) and down-regulation (TNC, CTGF, ICAM1) of several genes related to cellular invasion and migration. High ID3 expression was associated with poor survival of patients with medulloblastoma as with seeding at presentation. These findings indicated that ID3 plays an important role in seeding of medulloblastoma and may be a target of therapeutic intervention for enhancing survival of the patients in the poor-prognostic group.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5326. doi:1538-7445.AM2012-5326