Abstract
Medulloblastoma is the most common malignant brain tumor in children. Folate receptor 1 (Folr1) was abundantly expressed in some epithelial malignancies. However the expression profile and the role of clinicopathological significance and therapeutic target potential in medulloblastoma still remain elusive. Currently we detected the expression of Folr1 in medulloblastoma and identified the diagnostic application by evaluating the clinical, pathological and neuroimaging values. Then we developed a target therapeutic compound with Folr1, which exhibited promising efficiency in treatment of medulloblastoma. Folr1 expression was up-regulated in medulloblastoma and positively correlated with percentage of Ki-67 and MMP9 labeling, pathological subtypes, serum Folr1 levels and CSF spreading on MRI. The level of serum Folr1 showed rational sensitivity and specificity in predicting histological subgroups. Strong Folr1 expression was recommended as the independent value regarding the prognosis of patients with medulloblastoma. Folr1 targeted therapy attenuated the tumor growth and metastasis with down-regulation of MMPs proteins and activation of apoptosis. Immunostaining analysis in the xenograft samples showed the decreased Ki-67 and MMP9 index providing the strong evidences that Folr1 targeted application can suppress the proliferation and invasion. Our findings uncovered in Folr1 a predictive candidate and therapeutic target for medulloblastoma.
Highlights
Medulloblastoma (MB) is the most common malignant brain tumor in children, accounting for about 20% of children with intracranial tumors [1, 2] and about 50% of patients with metastasis along the leptomening via circulation of cerebrospinal fluid (CSF) [3]
Folate receptor 1 (Folr1) expression was up-regulated in medulloblastoma and positively correlated with percentage of Ki-67 and Matrix Metalloproteinase-9 (MMP9) labeling, pathological subtypes, serum Folr1 levels and CSF spreading on magnetic resonance image (MRI)
The correlation between Folr1 expression and clinical features, pathological features (Ki-67, MMP9 labeling and subtypes) as well www.impactjournals.com/oncotarget as neuroimaging features was further analyzed
Summary
Medulloblastoma (MB) is the most common malignant brain tumor in children, accounting for about 20% of children with intracranial tumors [1, 2] and about 50% of patients with metastasis along the leptomening via circulation of CSF [3]. Children who are more than 3 years old with the focal tumor at first diagnosis and the less than 1.5 cm residual tumor after operation will be classified in the average-risk group [8, 9] These features are only involved in the postsurgical prognosis and so far no items in blood or tissue samples have been regarded as the non-invasive biomarkers at the early stage. Based on the unique high expression of Folr in malignancies and restricted expression in normal tissues, cytarabine (Ara-C) binding to folic acid (FA) has been developed as a targeted therapeutic compound which can be delivered into tumor cells through its recognition and combination with Folr in our previous study [21]. The recent research throws light on the diagnostic and prognostic value of Folr, as well as the therapeutic implications of Folr1-Ara-C on MB
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