Serum amyloid A (SAA) and cancer: biological effects and mechanisms of action on glioblastomas multiformes

• Grant number: 11/00469-3
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2011
• End date: August 31, 2013
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Ana Campa
• Grantee: Ana Campa
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The acute phase protein serum amyloid A (SAA) is known to modulate inflammatory processes and has been described as the newest marker of tumor progression. This is because studies have shown increased serum levels of SAA in human malignancies. This finding is supported also by the fact that SAA is produced continuous and tenuously in chronic disorders and these contribute to the genesis and progression of tumors. As a new approach our goal has been to assess the direct effect of SAA on two strains of human glioblastomas (master's thesis FAPESP No. 07/56864-2). Working with A172 and T98G lineages we showed that SAA affects the production of cytokines and other factors related to the growth and spread of tumors (MMPs and RECK). Our investigations also helped confirm that glioblastomas are able to express and produce the protein SAA. The effects of SAA on the growth, migration and invasion depended on the strain and concentration of protein and suggest that SAA is important for the biology of tumors, acting both as pro and anti-neoplastic. Therefore, this project intended to analyze the effect of SAA on the cell cytoskeleton and focal adhesions, enzymatic activity of MMPs, cell cycle, apoptosis and necrosis, signalling pathways, receptors and production of reactive oxygen species (ROS). Finally we will also study the effect of hypoxia on the production of SAA by the tumor cells. We also intend to identify inducers of SAA in tumors and also assess the impact of overexpression and suppression of SAA in them. This study will permit to recognize the mechanisms by which SAA acts on tumor cells, an autocrine action for this protein and will contribute to the understanding of how inflammatory processes hold the tumor progression. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

KNEBEL, FRANCIELE HINTERHOLZ; UNO, MIYUKI; GALATRO, THAIS F.; BELLE, LUZIANE POTRICH; OBA-SHINJO, SUELI MIEKO; MARIE, SUELY KAZUE N.; CAMPA, ANA. Serum amyloid A1 is upregulated in human glioblastoma. JOURNAL OF NEURO-ONCOLOGY, v. 132, n. 3, p. 383-391, MAY 2017. (11/00469-3)