Evaluation of in vitro modulatory effect of the C-terminus of protein S100A9 on the growth of the tumoral cell lineage LLC walker 256 and on the proliferation and migration of thymic endothelial cells (tEnd.1)

• Grant number: 13/01295-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2013
• End date: May 27, 2015
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Renata Giorgi
• Grantee: Natassja Foizer Moraes
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Our group demonstrated that both S100A9 and a synthetic peptide identical to the C-terminal portion of murine S100A9 (mS100A9p) induced an antinociceptive effect in inflammatory pain models. In addition, mS100A9p inhibited the functions of mouse adherent peritoneal cells, which are critical for interaction with both malignant and stromal cells in tumor microenvironment. Tumor growth does not depend just on tumor cells, but also on interactions of cancer cells with the extracellular matrix, endothelial cells and stromal cells, resulting in metastasis. The complex formed between the proteins S100A8 and S100A9 has been constantly associated to malignancy in the literature. Thus, in vitro assays demonstrated that this complex in high concentrations 20-250 µg/ml (approximately 1-10 µM) inhibited the growth of different mouse and human tumor cell lines, besides promoting cytotoxicity and apoptosis of these cells. Despite these evidences, the action of mS100A9p has not been investigated so far on angiogenesis and tumor progression. Thus, the aim of this study was to evaluate the in vitro effect of mS100A9p on events involved in angiogenesis and tumor growth. On that account, thymic endothelial cells (tEnd.1) were used to study the effect of mS100A9p on angiogenesis, using in vitro assays of cell proliferation, migration (wound healing and transwell migration), adhesion (to type I collagen, fibronectin and laminin) and tube formation. In addition, the tumor cell line LLC Walker 256 was used to evaluate in vitro tumor progression using assays of cell proliferation, migration by the method of wound healing, and adhesion to different extracellular matrix components. The results showed that mS100A9p inhibited all the parameters related to the growth of new vessels. In regard to tumor progression, mS100A9p was shown to inhibit the proliferation, migration and adhesion of LLC cells to laminin, however it increased the adhesion of LCC cells to type I collagen and fibronectin. In conclusion, our data demonstrated that mS100A9p inhibited in vitro events involved in angiogenesis and tumor progression. Furthermore, besides inhibiting the function of inflammatory cells, mS100A9p interfered in neovascularization and tumor development. Thus, mS100A9p may be considered a good tool for the study of angiogenesis and tumor progression, and to have a possible therapeutic application in these processes. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MORAES, Natassja Foizer. The C-terminus of the murine protein S100A9 modulates the events involved in angiogenesis and tumor progression using in vitro models. 2015. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina Veterinária e Zootecnia (FMVZ/SBD) São Paulo.