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Dynamic Interplay in Tumor Ecosystems: Communication between Hepatoma Cells and Fibroblasts.

Gábor Petővári1, Gábor Tóth2, Lilla Turiák2

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International Journal of Molecular Sciences
|September 28, 2023
PubMed
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Cancer cells and fibroblasts communicate differently depending on tumor type. This interaction influences tumor progression, with potential for early liver cancer diagnosis via specific microRNAs.

Keywords:
cell communicationextracellular vesiclefibroblasthepatoma cellinvasionmetabolismmiRNAstromatumor

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Area of Science:

  • Cancer Biology
  • Cellular Communication
  • Tumor Microenvironment

Background:

  • Tumors are complex ecosystems involving cancer cells and stromal cells like cancer-associated fibroblasts (CAFs).
  • Interactions between cancer cells and CAFs are crucial for tumor progression and can vary based on cancer type.

Purpose of the Study:

  • To investigate the communication dynamics between poorly differentiated (HLE) and well-differentiated (HuH7) hepatoma cells and LX2 fibroblasts.
  • To explore various communication pathways including soluble factors, metabolites, extracellular vesicles (EVs), and microRNAs (miRNAs).

Main Methods:

  • Co-culture systems of hepatoma cell lines (HLE, HuH7) with LX2 fibroblasts.
  • Analysis of extracellular matrix components, integrin expression, matrix metalloproteinase (MMP) activity, and signaling pathway activation (MAPK, Wnt).
  • Characterization of extracellular vesicles (EVs) and their miRNA cargo.

Main Results:

  • HLE/LX2 co-culture led to increased laminin β1, collagen IV, CD44, and syndecan-1 shedding; HuH7/LX2 co-culture showed dominant fibronectin, thrombospondin-1, collagen IV, and cell surface syndecan-1.
  • Differential integrin and MMP expression was observed based on hepatoma cell differentiation.
  • Reciprocal activation of MAPK and Wnt signaling occurred between hepatoma cells and LX2 fibroblasts via direct contact and EVs; LX2-derived EVs upregulated SPOCK1 in hepatoma EVs.
  • Liver cancer-specific miRNAs were identified in hepatoma EVs.

Conclusions:

  • Hepatoma cell differentiation dictates specific communication patterns with fibroblasts, impacting the tumor microenvironment.
  • EV-mediated communication plays a significant role in regulating signaling pathways and cargo exchange between cancer cells and fibroblasts.
  • Identified liver cancer-specific miRNAs in EVs may hold potential for early cancer diagnosis, warranting further investigation.