Autologous antibody to src-homology 3-domain GRB2-like 1 specifically increases in the sera of patients with low-grade gliomas.
BACKGROUND
Glioma is the most common primary malignant central nervous system tumor in adult, and is usually not curable in spite of various therapeutic approaches. Clarification of the oncogenic process in its early stage is important for the diagnosis and effective therapy.


METHODS
In the present study, we used the serological identification of antigens by recombinant cDNA expression cloning (SEREX) to explore the subtle changes of the protein expression in low-grade glioma. The levels of serum autoantibodies to the SEREX-identified glioma-related antigens were analyzed by ELISA, and the epitope site was identified using deletion mutants and overlap peptide array. Changes in the serum autoantibody levels were examined in the rat glioma model using C6 and 9 L glioma cell lines.


RESULTS
We identified 31 glioma-related antigens by SEREX. Among them, the serum level of autoantibody to src-homology 3-domain GRB2-like 1 (SH3GL1) was significantly higher in patients with low-grade glioma than healthy volunteers or high-grade gliomas. The 10 amino-acids at the C-terminal were identified as the epitope site by the overlap peptide array and the ELISA using deletion mutants. The tissue expression of SH3GL1 protein increased in proportion to glioma progression. The rat glioma models confirmed the increase of anti-SH3GL1 autoantibody level in the early stage and the suppression in the late stage.


CONCLUSIONS
SH3GL1 may be involved in the oncogenic process of gliomas and effectively elicit an autologous antibody response in low-grade gliomas. The immunological reaction to SH3GL1 would contribute to the establishment of a novel diagnostic and therapeutic target for gliomas.
Departments of Neurological Surgery, Chiba University, Graduate School of Medicine, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan.
Tomoo
T
Matsutani
Takaki
T
Hiwasa
Masaki
M
Takiguchi
Takashi
T
Oide
Mitoshi
M
Kunimatsu
Naokatsu
N
Saeki
Yasuo
Y
Iwadate
D000818:Animals; D000906:Antibodies / Q000097:blood* / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D001932:Brain Neoplasms / Q000097:blood / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology; D015723:Gene Library; D005910:Glioma / Q000097:blood / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D060787:Neoplasm Grading; D051381:Rats; D015203:Reproducibility of Results
D000906:Antibodies; D000951:Antigens, Neoplasm; D000939:Epitopes; D047908:Intracellular Signaling Peptides and Proteins; C105159:SH3GL1 protein, human