Phd Candidate in Liver Cancer Biology
il y a 2 semaines
**Impact of sympathetic autonomic innervation of the tumor microenvironment on the progression of human hepatocellular carcinoma.**
Hepatocellular carcinoma (HCC) is the second deadliest cancer worldwide. It has been classified by the French National Cancer Institute (INCa) as a poor-prognosis cancer, with a 5-year survival rate of less than 33%. The chronic fibroinflammatory liver disease background leads to increased innate immune reactivity and extracellular matrix remodeling.1 This microenvironment sets the stage for the emergence of cancer stem/progenitor cells.
HCCs are generally highly cellular tumors, with a soft consistency on macroscopic examination and little intratumor fibrosis. However, within certain HCCs, fibro-inflammatory foci may be distinguished on microscopic examination. These foci are composed of extracellular matrix, cancer-associated fibroblasts, immune cells and growth factors and have been called _"Fibrous Nests."_2-3 HCCs containing fibrous nests are enriched in cancer stem/progenitor cells, WNT/TGFB signals;2-3 and their proteomic signatures;4-5 indicate that they belong to the most aggressive class of HCCs, known as ECM/STEM.6-7
Intra-tumor fibrosis in HCCs may be linked to an immunosuppressive environment and to a presence of sympathetic nerve endings at the tumor invasion front. In this microenvironment, cancer-associated fibroblasts, neo-formed sympathetic nerve endings and the extracellular matrix could exert mechanical forces activating pro-tumor signals leading to the amplification of cancer stem/progenitor cell populations and tumor invasion.
Our project aims to assess the impact of intra-tumor fibrosis and its sympathetic innervation on HCC progression. The hallmarks of this three-year PhD project include prognostic evaluation of fibrosis and sympathetic innervation in 200 HCC cases (project approved by the INSERM Ethics Committee), analysis of the mechanical forces therein, affected signaling networks, and in vitro modeling of mechanical forces under defined adrenergic environments and extracellular matrix compositions.
**References**:
1. JHEP Reports (2023), 6 :100936
2. Oncotarget (2016), 7:39026
3. Int J Biochem Cell Biol (2016), 81(Pt A):195
4. Hepatology (2023), 78: 741
5. Hepatology (2023), 78:691
6. Hepatology (2017), 66:1502
7. World journal of Gastroenterology (2018), 24:4536
**Job Types**: Full-time, Internship, Contract
Contract length: 36 months
**Salary**: From 1,800.00€ per month
Work Location: Hybrid remote in 35033 Rennes
Application Deadline: 03/06/2024
Expected Start Date: 01/10/2024
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