ID3 contributes to cerebrospinal fluid seeding and poor prognosis in medulloblastoma

BMC Cancer

Ji Hoon Phi⁴  Seung Ah Choi³  Sang-Hee Lim³  Joongyub Lee²  Kyu-Chang Wang³  Sung-Hye Park¹  Seung-Ki Kim⁴ 

[1] Department of Pathology, Seoul National University Children’s Hospital, Seoul, Republic of Korea

[2] Medical Research Collaborating Center, Seoul National University Hospital, Seoul, Republic of Korea

[3] Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, Seoul, Republic of Korea

[4] Adolescent Cancer Center, Seoul National University Cancer Hospital, Seoul, Republic of Korea

关键词: Group 4;    Survival;    Prognosis;    Seeding;    Medulloblastoma;    ID3;   

Others  :  1079699
DOI  :  10.1186/1471-2407-13-291

 received in 2012-07-10, accepted in 2013-05-29,  发布年份 2013

【 摘 要 】

Background

The inhibitor of differentiation (ID) genes have been implicated as promoters of tumor progression and metastasis in many human cancers. The current study investigated the expression and functional roles of ID genes in seeding and prognosis of medulloblastoma.

Methods

ID gene expression was screened in human medulloblastoma tissues. Knockdown of ID3 gene was performed in medulloblastoma cells in vitro. The expression of metastasis-related genes after ID3 knockdown was assessed. The effect of ID3 knockdown on tumor seeding was observed in an animal model in vivo. The survival of medulloblastoma patients was plotted according to the ID3 expression levels.

Results

Significantly higher ID3 expression was observed in medulloblastoma with cerebrospinal fluid seeding than tumors without seeding. Knockdown of ID3 decreased proliferation, increased apoptosis, and suppressed the migration of D283 medulloblastoma cells in vitro. In a seeding model of medulloblastoma, ID3 knockdown in vivo with shRNA inhibited the growth of primary tumors, prevented the development of leptomeningeal seeding, and prolonged animal survival. High ID3 expression was associated with shorter survival of medulloblastoma patients, especially in Group 4 medulloblastomas.

Conclusions

High ID3 expression is associated with medullolbastoma seeding and is a poor prognostic factor, especially in patients with Group 4 tumors. ID3 may represent the metastatic/ aggressive phenotype of a subgroup of medulloblastoma.

【 授权许可】

   
2013 Phi et al.; licensee BioMed Central Ltd.

【 图 表 】

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