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H2020Individual fellowship2017–2019

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

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2017-07-01 → 2019-06-30
EU contribution
€160,636
Participants
1
Scheme
MSCA-IF-EF-ST

Lines connect the coordinator with its partners.

Results in brief

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

Oncologic diseases are multifactorial pathologies involving intricate cell-cell communication networks, in which by interplaying with healthy host cells tumors disseminate pro-tumorigenic messages creating a systemic tumor environment, or macroenvironment, which is key for malignant progression. Thus, deciphering the mechanisms that mediate cell-cell communication between transformed and non-transformed cells is of key significance, as it has the potential to significantly improve the diagnosis and treatment of oncologic patients. Extracellular vesicles, such as exosomes (exo), are produced by virtually all cells and are emerging cell-cell communication players in physiological and pathological scenarios. As exo can carry and transfer packages of information from cell to cell, locally and to distant cellular targets by traveling though the peripheral circulation, they have been used as liquid biopsies for both oncologic and non-oncologic diseases. We have recently shown that tumor-derived exo can induce microenvironments supportive of tumor growth and metastasis, such as pre-metastatic niches that precedes and support metastatic seeding, by acting in non-tumor cells. However, we still have insufficient information on how to detect the formation of pre-metastatic microenvironments (such as liver pre-metastatic niches – LPMN) in clinical settings. We here proposed that the characterization of stroma-derived exo present in biologic fluids has the potential to offer a non-invasive alternative to detect and characterize tumor-associated microenvironments, such as LPMNs. In addition, we proposed to test whether liver-derived exo play a role in supporting metastatic Pancreatic Cancer (PC) lesions grow in the liver. For that we proposed to: - Evaluate whether overall production and content of liver-derived exo are modified during LPMN formation; - Identify new exosomal biomarkers for the detection of LPMN formation; - Test whether liver-derived exo interact with PC cells and play a role in supporting liver metastasis.

Data: CORDIS, © European Union

Project 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.

Original text from CORDIS.

Participants

  • FUNDACAO D. ANNA DE SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD · LISBOACoordinatorPortugal

Links

Data: CORDIS, © European Union