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.
