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

Abstract

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.

EI24 Inhibits Cell Proliferation and Drug Resistance of Esophageal Squamous Cell Carcinoma

“…Inflammatory response dysfunction had been identified to be strongly connected to the pathogenesis and progression of cancers ( 34 ). Notably, certain acute phase response signaling pathway-related genes, such as fibrinogen α chain (FGA) and serum amyloid a (SAA), were reported to be associated with malignant phenotypes of tumors, and their expressions dysregulated on account of EI24 overexpression ( 35 , 36 ). Moreover, inflammation response has great potential to induce cell cycle arrest and inhibit cellular proliferation ( 37 ).…”

Targeting Fluorescence Imaging of RGD-Modified Indocyanine Green Micelles on Gastric Cancer

“…Now more and more evidence shows that integrins expressed by endothelial cells regulate cell migration and survival during angiogenesis, while integrins expressed by cancer cells enhance metastasis by promoting invasion and movement across blood vessels (Weis and Cheresh, 2011;Nieberler et al, 2017). Integrin α v β 3 is over-expressed on neoplastic tumor blood vessels and some tumor cells, playing an important role in proliferation, metastasis, and invasion of cancer cells (Kwakwa and Sterling, 2017;Lin et al, 2018). A study on integrin α v β 3 in GC cancer reveals that it is expressed widely in at least one tumor component and may be helpful in the routine classification of GC subtypes (Boger et al, 2015).…”

Influence of gene expression on survival of clear cell renal cell carcinoma

“…75 Serum Amyloid A1, SAA1, is an apolipoprotein that is highly expressed in response to inflammation and tissue injury. It is overexpressed in glioblastoma (GBM), 76,77 cervical carcinoma, 78 NSCLC, 79 AML, 80 and gastric cancer 81 and associated with progression and poor prognosis in these cancers.…”