Serum amyloid A1 in combination with integrin αVβ3 increases glioblastoma cells mobility and progression

Autor: Ching‐Yu Lin, Shun‐Tai Yang, Shing‐Chuan Shen, Yi‐Chen Hsieh, Fei‐Ting Hsu, Cheng‐Yu Chen, Yung‐Hsiao Chiang, Jian‐Ying Chuang, Kai‐Yun Chen, Tsung‐I Hsu, Wan‐Chong Leong, Yu‐Kai Su, Wei‐Lun Lo, Yi‐Shian Yeh, Yudha Nur Patria, Hsiu‐Ming Shih, Che‐Chang Chang, Szu‐Yi Chou
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Molecular Oncology, Vol 12, Iss 5, Pp 756-771 (2018)
Druh dokumentu: article
ISSN: 1878-0261
1574-7891
DOI: 10.1002/1878-0261.12196
Popis: Glioblastoma multiforme (GBM) is a highly malignant type of brain tumor found in humans. GBM cells reproduce quickly, and the median survival time for patients after therapy is approximately 1 year with a high relapse rate. Current therapies and diagnostic tools for GBM are limited; therefore, we searched for a more favorable therapeutic target or marker protein for both therapy and diagnosis. We used mass spectrometry (MS) analysis to identify GBM‐associated marker proteins from human plasma and GBM cell cultures. Additional plasma and 52 brain tissues obtained from patients with gliomas were used to validate the association rate of serum amyloid A1 (SAA1) in different grades of gliomas and its distribution in tumors. Microarray database analysis further validated the coefficient of SAA1 levels in gliomas. The cellular mechanisms of SAA1 in GBM proliferation and infiltration were investigated in vitro. We analyzed the correlation between SAA1 and patients' medication requirement to demonstrate the clinical effects of SAA1 in GBM. SAA1 was identified from MS analysis, and its level was revealed to be correlated with the disease grade, clinical severity, and survival rate of patients with gliomas. In vitro cultures, including GBM cells and normal astrocytes, revealed that SAA1 promotes cell migration and invasion through integrin αVβ3 to activate the Erk signaling pathway. Magnetic resonance imaging and tumor region‐specific microarray analysis identified a correlation between SAA1 and GBM cell infiltration in patients. In summary, our results demonstrate that SAA1 in combination with integrin αV and β3 can serve as an indicator of high glioblastoma risk. We also identified the cellular mechanisms of SAA1 contributing to GBM progression, which can serve as the basis for future GBM therapy.
Databáze: Directory of Open Access Journals
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