KEY TAKEAWAYS
- The study aimed to explore how CAFs within the liver TME influence cancer progression by interacting with other cells.
- Researchers noticed that F5-CAFs support liver cancer progression by enhancing cancer stem cell survival.
Cancer-associated fibroblasts (CAFs) are a crucial cell type within the tumor microenvironment (TME) and have been identified in multiple tumors. Despite this, the specific spatial coordination between CAFs and other cell populations within the liver TME and their role in promoting liver cancer progression remains unclear.
Si-yu Jing and the team aimed to investigate how CAFs interact with and influence other cellular components in the liver TME to drive cancer progression.
Researchers combined multi-region proteomics (6 patients, 24 samples), 10X Genomics Visium spatial transcriptomics (11 patients, 25 samples), and multiplexed imaging (92 patients, 264 samples) to explore expression patterns and spatial relationships. A newly identified CAF subpopulation was further validated through cells isolated from 5 patients with liver cancer and tested in in vitro functional assays, confirming its role in cancer progression.
The results identified a liver CAF subpopulation named F5-CAF, marked by the expression of COL1A2, COL4A1, COL4A2, FSTL1 and CTGF. F5-CAF is usually found around tumor nests in hepatocellular carcinoma (HCC), often colocalizing with cancer cells with higher stemness. In 91 patients and a bulk transcriptome of 371 patients, F5-CAF presence was linked to a worse prognosis. Further lab tests confirmed that F5-CAFs from patients with liver cancer can boost the proliferation and stemness of HCC cells.
The study concluded that the F5-CAF subpopulation in liver cancer is linked to cancer stemness and poor prognosis, highlighting its role in promoting liver cancer progression by supporting cancer stem cell survival.
The study was funded by the National Key R&D Program of China.
Source: https://pubmed.ncbi.nlm.nih.gov/39138551/
Jing SY, Liu D, Feng N, et al. (2024). “Spatial multiomics reveals a subpopulation of fibroblasts associated with cancer stemness in human hepatocellular carcinoma.” Genome Med. 2024 Aug 13;16(1):98. doi: 10.1186/s13073-024-01367-8. PMID: 39138551.
