The role of a disintegrin and metalloproteinase 9 (ADAM9) in breast cancer metastasis to bone and soft tissues: the participation of lymph nodes

• Grant number: 12/08563-1
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: August 10, 2012
• End date: February 09, 2013
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Heloisa Sobreiro Selistre de Araújo
• Grantee: Kelli Cristina Micocci
• Supervisor: Normand Pouliot
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Institution abroad: University of Melbourne, Australia
• Associated to the scholarship: 10/10201-5 - The role of ADAM9 on tumor spreading via lymphatic system: a possible pharmacological target, BP.DR

Abstract

Metastasis results from a complex molecular cascade through which cancer cells leave the site of the primary tumor and disseminate to distant sites, and in these new sites this cells will go to proliferate and form secondary tumor foci, this is the main cause of morbidity and mortality in cancer patients. The ADAMs (A Disintegrin And Metalloprotease) is a class of multi-functional membrane proteins. They play important roles in many physiological processes as in fertilization, myoblast fusion, migration, proliferation and cell survival, as well in diseases including breast, prostate, pancreas, liver, kidneys and skin cancer. An important member of this family is the ADAM9 protein, it is involved in cellular processes such as adhesion, migration and signaling of tumor cells and it is involved in the metastatic spreading. Previous results obtained in our lab evidence the involvement of ADAM9 in tumor invasion, because when this protein was silencing with siRNAADAM9 the invasion in matrigel was inhibited in approximately 70% when compared to control, suggesting that ADAM9 is an important molecule in the processes of invasion and metastasis. The project aims to learn the technique and to accomplish the knockout ADAM9 using short hairpin RNA (short hairpin RNA- shRNA) in breast tumor cell lines of varying metastatic potential belonging to Dr. Normand's Laboratory of Metastasis, in renowned Peter MacCallum Cancer Centre. In addition, to examine the impact of ADAM9 downregulation in some assays in vitro (survival, proliferation, migration and invasion) and in a syngenic mouse model of spontaneous breast cancer metastasis, and evaluating the contribution of ADAM9 to lymphatic spread, bone and soft tissues, among them lungs. Thus, the results will help elucidate the mechanisms involved in the tumor spread more accurately, because will be used an animal model of metastasis formation, mimicking the more accurate this disease in human. Finally, the research and results will bring important contributions to find antimetastatic new tools. (AU)