Summary
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.
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/751547 |
| Start date: | 01-07-2017 |
| End date: | 30-06-2019 |
| Total budget - Public funding: | 160 635,60 Euro - 160 635,00 Euro |
Cordis data
Original description
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.Status
CLOSEDCall topic
MSCA-IF-2016Update Date
28-04-2024
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