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Phenotypic characterization of Liver-derived exosomes populations associated with liver metastasis in pancreatic cancers

Phenotypic characterization of Liver-derived exosomes populations associated with liver metastasis in pancreatic cancers

Objective

Tumors are not isolated entities, but complex systemic networks involving cell-cell communication between transformed and non-transformed cells. The milieu created by tumor-associated cells may either support or halt tumor progression. Non-tumor cells also play a role at distant sites, preparing future metastatic sites to support engraftment and survival of metastatic cells. In addition to cell-cell contact, cells communicate through secreted factors via a highly complex system involving characteristics such as ligand concentration, receptor expression and integration of diverse signaling pathways. Of these, extracellular vesicles such as exosomes are emerging as novel cell-cell communication players in physiological and pathological scenarios. We recently described that exosomes produced by highly metastatic pancreatic cancers (PC) induce Liver Pre-Metastatic Niches (LPMN) supportive of hepatic metastasis. Although we defined how LPMN are induced by PC-derived exosomes, the specific mechanism of how the LPMN support the formation and progression of liver metastatic lesions is still unknown. In addition, while we have been showing that pre-metastatic niches support metastatic spreading, we still do not have appropriate means to detect the formation of these niches by non-invasive methods in clinical settings. Thus we propose to: 1)Characterize the composition of liver-derived exosomes populations in physiologic and LPMN-associated settings by applying state-of-the-art flow cytometry tailored to nanoparticles analysys at a single-exosome level; 2)Test whether liver-derived exosomes interact with metastatic PC cells and play a role in supporting the progression of PC metastatic lesions in the liver. This project has the potential to offer not only a non-invasive alternative to detect and characterize tumor-associated microenvironments, such as LPMN, but also opportunities for novel therapeutic approaches to target pro-tumorigenic cell-cell communication.

Coordinator

FUNDACAO D. ANNA SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD

Address

Avenida Brasilia Centro De Investigacao Da Fundacao Champ Alimaud
1400 038 Lisboa

Portugal

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 160 635,60

Project information

Grant agreement ID: 751547

Status

Ongoing project

  • Start date

    1 July 2017

  • End date

    30 June 2019

Funded under:

H2020-EU.1.3.2.

  • Overall budget:

    € 160 635,60

  • EU contribution

    € 160 635,60

Coordinated by:

FUNDACAO D. ANNA SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD

Portugal