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.


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.
Department of Dental Hygiene, College of Health Science, Eulji University, 553 Sansung-Daero, Soojung-Gu, Seongnam 461-713, Republic of Korea. Electronic address: kiteys@eulji.ac.kr.
Young Sun
YS
Hwang
Oral Cancer Research Institute, Department of Oral Biology, and BK21 PLUS Project, Yonsei University College of Dentistry, Seoul 120-752, Republic of Korea; The Applied Life Sciences, Graduate School, Yonsei University, Seoul 120-749, Republic of Korea.
Kwang-Kyun
KK
Park
Oral Cancer Research Institute, Department of Oral Biology, and BK21 PLUS Project, Yonsei University College of Dentistry, Seoul 120-752, Republic of Korea; The Applied Life Sciences, Graduate School, Yonsei University, Seoul 120-749, Republic of Korea. Electronic address: wychung@yuhs.ac.
Won-Yoon
WY
Chung
D000818:Animals; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D018920:Coculture Techniques; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000378:metabolism; D064593:Heterografts; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D010641:Phenotype; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D059016:Tumor Microenvironment; D000098853:Podoplanin
D008562:Membrane Glycoproteins; D053773:Transforming Growth Factor beta1; C490441:Pdpn protein, mouse; D000098853:Podoplanin
Fibroblast; Invasion; Podoplanin; Stromal; Transforming growth factor β1; Xenograft