Exosomes released by pre-metastatic NICHE-CONTAINING liver as mediators of pancreas adenocarcinoma liver metastasis

• Grant number: 19/00740-0
• Support type: Scholarships abroad - Research
• Effective date (Start): April 01, 2019
• Effective date (End): March 15, 2020
• Field of knowledge: Biological Sciences - Morphology
• Principal Investigator: Andréia Hanada Otake
• Grantee: Andréia Hanada Otake
• Host: Bruno Costa da Silva
• Home Institution: Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira (ICESP). Coordenadoria de Serviços de Saúde (CSS). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Local de pesquisa : Fundação Champalimaud, Portugal

Abstract

Pancreatic ductal adenocarcinomas (PDAC) are highly aggressive tumors and patients are diagnosed in late stages, presenting a median survival of about six months. Usually, advanced cases of PDAC present metastatic foci in the liver which are resistant to conventional therapies. Studies have shown that metastasis establishment is dependent on pre-metastatic niche (PNM) formation. PMNs lead to host tissue alterations which determine tumor cells recruitment and metastasis growth. More recently, exosomes released by pancreatic tumor cells were demonstrated to be functional contributors in establishing liver PMNs. However, there is no evidence whether exosomes released by a liver containing PMN (PMN-exo), before tumor cells colonization, have a role in the establishment and growth of metastasis. Preliminary data have shown that PMN-exo profile is different from that released by healthy liver. Therefore, this project aims to investigate whether PMN-exos act as mediators of development of sustained liver metastasis. In this context, we aim to investigate protein cargo in PMN-exo as potential markers and then, anticipate PMN formation and metastasis. Next, we plan to investigate whether these proteins can be detected in exosomes from mice plasma and then evaluate their expression in nanoparticles cytometer. The host group has expertise in development of projects involving exosome studies as well in evaluating exosomes populations.