Serum amyloid A1 is upregulated in human glioblastoma

Abstract

Serum amyloid A1 (SAA1) is a sensitive acute phase reactant primarily produced by the liver in response to acute inflammation. We have recently shown that SAA affects proliferation, migration, and invasion of glioblastoma cell lines, which suggest its participation in the malignant process. Consistently, levels of SAA have been used as a non-invasive biomarker for the prognosis of many cancers. In this study, we aimed to investigate SAA serum levels and expression of SAA genes in human astrocytomas tissues. Serum and tissue samples were obtained from patients with astrocytoma grades I to III and glioblastoma (GBM or grade IV). Levels of circulating SAA were significantly higher in the serum of patients with AGII-IV when compared to non-neoplastic samples derived from non-neoplastic patients (NN) (p > 0.0001). Quantitative real time PCR (qRT-PCR) of 148 astrocytomas samples (grades I-IV) showed that SAA1 mRNA was significantly higher in GBM when compared to AGI-III and NN samples (p < 0.0001). Immunohistochemistry analysis revealed cytoplasmic positivity for SAA in GBM. There was no correlation of SAA1 with clinical end-point of overall survival among GBM patients. However, it was found a positive correlation between SAA1 and genes involved in tumor progression, such as: HIF1A (r = 0.50; p < 0.00001), CD163 (r = 0.52; p < 0.00001), CXCR4 (r = 0.42; p < 0.00001) and CXCR7 (r = 0.33; p = 0.002). In conclusions, we show that astrocytoma patients have increased levels of serum SAA and SAA1 is expressed and secreted in GBM, and its co-expression with tumor-related genes supports its involvement in GBM angiogenesis and progression.

Serum amyloid A – a review

“…Knebel et al (2017) found that SAA1 was both expressed and secreted by human glioblastoma cells. SAA production was associated with tumor associated macrophages of the M2 type.…”

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

“…The correlation of SAA1 with human glioblastomas was proposed in a recent study (Knebel et al ., ). The study revealed that SAA1 was upregulated 10 to 60 times in patients with glioblastomas compared with patients with non‐neoplastic and other grades of astrocytoma.…”

“…Knebel et al . () also found that serum levels of SAA1 were associated with the grades of gliomas but did not affect the clinical outcomes of patients with GBM. By contrast, we found that the gene expression levels of SAA1 in brain tumors were associated with glioma malignancy and patient mortality at threshold 25 (Fig.…”

“…In addition to glioma cells, SAA1 induced the migration of normal astrocytes (Fig. E–H) and has been shown to promote angiogenesis in nasopharyngeal carcinoma and GBM (Knebel et al ., ; Lung et al ., ). Given the observation that SAA1 can be shed by tumor cells and reach the plasma, SAA1 may recruit peripheral immune cells such as macrophages and monocytes into the tumor microenvironments.…”

“…However, the role of SAA1 in gliomas remains unclear. Knebel et al (2013) revealed SAA1 to have a dual role in glioma migration regulation, although the mechanism is unclear, and upregulated SAA1 levels in human glioblastomas were suggested to create a high-inflammation microenvironment (Knebel et al, 2017).…”