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-β1 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-β1 induced PDPN expression by Transwell invasion and influenced tumour growth in orthotopic xenografts. Results Stimulation by TGF-β1 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 TβRII-dependent. Tumour growth of HSC-2 OSCC in a mouse xenograft was intensified in the tumour CAF microenvironment. Conclusions Stromal TGF-β1 signalling promoted PDPN expression in cancer cells, thereby enhancing tumour growth and leading to a more invasive phenotype.
Bibliographical noteFunding Information:
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2012R1A1A2040564 ).
All Science Journal Classification (ASJC) codes
- Cell Biology