Current Protein & Peptide ScienceCurrent Protein & Peptide ScienceCurrent Protein & Peptide Science1389-20371875-5550Bentham Science64549610.2174/1389203724666230825100318Life SciencesResearch ArticleIntercellular Interactions Mediated by HGF And TGF-Β Promote the 3D Spherical and Xenograft Growth of Liver Cancer CellsTongHaiboinfo@benthamscience.netGuoDongweiinfo@benthamscience.netLuoYiinfo@benthamscience.netHuangShigaoinfo@benthamscience.netPengZhenginfo@benthamscience.netLvXiaolaninfo@benthamscience.netZhangPengfeiinfo@benthamscience.netChenQiaoinfo@benthamscience.netZhangHongyuinfo@benthamscience.netChenJianlininfo@benthamscience.netMaXingxuaninfo@benthamscience.netOuyangBohuiinfo@benthamscience.netHaoMenginfo@benthamscience.netFaculty of Health Sciences, University of MacauDepartment of Pulmonary and Critical Care Medicine, Liuzhou Traditional Chinese Medical HospitalDepartment of Neurosurgery, Liuzhou Traditional Chinese Medical HospitalDepartment of Radiation Oncology, The First Affiliated Hospital, Air Force Medical UniversityDepartment of Clinical Laboratory, Liuzhou Traditional Chinese Medical HospitalDepartment of Clinical Laboratory, Liuzhou Maternity and Child Healthcare HospitalDepartment of gastroenterology, Liuzhou Traditional Chinese Medical HospitalShengli Clinical Medical College, Fujian Medical University01012024251718211012025Copyright ©; 2024, Bentham Science Publishers2024Bentham Science Publishershttps://journals.eco-vector.com/1389-2037/article/view/645496

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

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