Stromal transforming growth factor-beta 1 is crucial for reinforcing the invasive potential of low invasive cancer.
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.
['Hwang|Young Sun|YS|', 'Park|Kwang-Kyun|KK|', 'Chung|Won-Yoon|WY|']
D000818:Animals D015153:Blotting, Western D002294:Carcinoma, Squamous Cell D018920:Coculture Techniques D018450:Disease Progression D004797:Enzyme-Linked Immunosorbent Assay D005347:Fibroblasts D064593:Heterografts D007150:Immunohistochemistry D008297:Male D008562:Membrane Glycoproteins D051379:Mice D008807:Mice, Inbred BALB C D008819:Mice, Nude D009062:Mouth Neoplasms D009361:Neoplasm Invasiveness D010641:Phenotype D015398:Signal Transduction D053773:Transforming Growth Factor beta1 D059016:Tumor Microenvironment
Stromal Invasion Xenograft Fibroblast Podoplanin Transforming growth factor β1