OBJECTIVE: Tumour cells alter the characteristics of the adjacent stroma to create a supportive microenvironment during cancer progression. In vitro and in vivo experiments were carried out to verify the role of stromal TGF-beta1 in reinforcing of the invasive potential in low invasive cancer. MATERIALS AND METHODS: Isolated NF or CAF was co-cultured with low invasive HSC-2 cells to evaluate whether stromal TGF-beta1 induced PDPN expression by Transwell invasion and influenced tumour growth in orthotopic xenografts. RESULTS: Stimulation by TGF-beta1 promoted PDPN expression and Transwell invasion through SMAD signalling as well as activation of Src, P38 mitogen activated protein kinase and extracellular regulated kinase 1/2. PDPN induction was TbetaRII-dependent. Tumour growth of HSC-2 OSCC in a mouse xenograft was intensified in the tumour CAF microenvironment. CONCLUSIONS: Stromal TGF-beta1 signalling promoted PDPN expression in cancer cells, thereby enhancing tumour growth and leading to a more invasive phenotype.
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