Dual Effect of Serum Amyloid A on the Invasiveness of Glioma Cells

Franciele Hinterholz Knebel,Renata Chaves Albuquerque,Ana Campa,Silvya Stuchi Maria-Engler,Renato Ramos Massaro

doi:10.1155/2013/509089

Abstract

Evidence sustains a role for the acute-phase protein serum amyloid A (SAA) in carcinogenesis and metastasis, and the protein has been suggested as a marker for tumor progression. Nevertheless, the demonstration of a direct activity of SAA on tumor cells is still incipient. We have investigated the effect of human recombinant SAA (rSAA) on two human glioma cell lines, A172 and T98G. rSAA stimulated the [3H]-thymidine incorporation of both lines, but had dual effects on migration and invasiveness which varied according to the cell line. In T98G, the rSAA increased migration and invasion behaviors whereas in A172 it decreased these behaviors. These findings agree with the effect triggered by rSAA on matrix metalloproteinases (MMPs) activities measured in a gelatinolytic assay. rSAA inhibited activity of both MMPs in A172 cells while increasing them in T98G cells. rSAA also affected the production of compounds present in the tumor microenvironment that orchestrate tumor progression, such as IL-8, the production of reactive oxygen species (ROS) and nitric oxide (NO). We also observed that both lines expressed all three of the isoforms of SAA: SAA1, SAA2, and SAA4. These data suggest that some tumor cells are responsive to SAA and, in these cases, SAA may have a role in cancer progression that varies according to the cell type.

Highlights

Serum amyloid A (SAA) is an acute-phase protein with cytokine-like properties produced predominantly by the liver [1, 2]
Given that the susceptibility to develop a glioma seems to be associated with genetic inflammatory patterns [23], we investigated the effect of recombinant SAA (rSAA) on the production of molecules involved in inflammation and tumor progression, such as the chemokine IL-8, nitric oxide (NO), and reactive oxygen species (ROS)
We have shown that SAA induced proliferation and affected migration and invasiveness of two human glioma cell lines

Summary

Introduction

Serum amyloid A (SAA) is an acute-phase protein with cytokine-like properties produced predominantly by the liver [1, 2]. The SAA gene family, composed by three isoforms (SAA1, SAA2, and SAA4), is upregulated in human tumors [4] This finding has prompted a number of clinical studies in which a direct correlation between high concentrations of SAA in the serum of cancer patients and their tumor grading has been investigated [4]. We investigated the effect of rSAA on the expression and activity of MMP2 and MMP-9 in two human glioma cell lines, A172 and T98G, and the correlation with cell proliferation, migration, and invasion. Given that the susceptibility to develop a glioma seems to be associated with genetic inflammatory patterns [23], we investigated the effect of rSAA on the production of molecules involved in inflammation and tumor progression, such as the chemokine IL-8, nitric oxide (NO), and reactive oxygen species (ROS). Our findings support a direct contribution of SAA to tumor development, progression, and metastasis that depends on the cell type and concentration of SAA

Materials and Methods

Results

Findings

Discussion