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Current Protein & Peptide Science

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ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

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General Research Article

Intercellular Interactions Mediated by HGF And TGF-Β Promote the 3D Spherical and Xenograft Growth of Liver Cancer Cells

Author(s): Zheng Peng, Xiaolan Lv, Pengfei Zhang, Qiao Chen, Hongyu Zhang, Jianlin Chen, Xingxuan Ma, Bohui Ouyang, Meng Hao, Haibo Tong, Dongwei Guo, Yi Luo* and Shigao Huang*

Volume 25, Issue 1, 2024

Published on: 27 September, 2023

Page: [71 - 82] Pages: 12

DOI: 10.2174/1389203724666230825100318

Price: $65

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Abstract

Background: Recently, the importance of the interactions between liver cancer cells and fibroblasts has been increasingly recognized; however, many details remain to be explored.

Methods: In this work, we first studied their intercellular interactions using conditioned medium from mouse embryonic fibroblasts (MEFs), then through a previously established coculture model.

Results: Culturing in a conditioned medium from MEFs could significantly increase the growth, migration, and invasion of liver cancer cells. The coculture model further demonstrated that a positive feedback loop was formed between transforming growth factor-β (TGF-β) from HepG2 cells and mHGF (mouse hepatocyte growth factor) from MEFs during coculture. In this feedback loop, c-Met expression in HepG2 cells was significantly increased, and its downstream signaling pathways, such as Src/FAK, PI3K/AKT, and RAF/MEK/ERK, were activated. Moreover, the proportion of activated MEFs was also increased. More importantly, the growth-promoting effects caused by the interaction of these two cell types were validated in vitro by a 3D spheroid growth assay and in vivo by a xenograft mouse model.

Conclusion: Collectively, these findings provide valuable insights into the interactions between fibroblasts and liver cancer cells, which may have therapeutic implications for the treatment of liver cancer.

Keywords: Hepatocyte growth factor, transforming growth factor-β, liver cancer cells, 3D spheroid, fibroblasts, coculture.

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