Young Sun Hwang1, Kwang-Kyun Park2, Won-Yoon Chung3. 1. 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. 2. 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. 3. 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.
Abstract
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.
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 tumourCAF microenvironment. CONCLUSIONS: Stromal TGF-β1 signalling promoted PDPN expression in cancer cells, thereby enhancing tumour growth and leading to a more invasive phenotype.
Authors: Judith A E M Zecha; Judith E Raber-Durlacher; Raj G Nair; Joel B Epstein; Stephen T Sonis; Sharon Elad; Michael R Hamblin; Andrei Barasch; Cesar A Migliorati; Dan M J Milstein; Marie-Thérèse Genot; Liset Lansaat; Ron van der Brink; Josep Arnabat-Dominguez; Lisette van der Molen; Irene Jacobi; Judi van Diessen; Jan de Lange; Ludi E Smeele; Mark M Schubert; René-Jean Bensadoun Journal: Support Care Cancer Date: 2016-03-16 Impact factor: 3.603
Authors: Jhon A Ochoa-Alvarez; Harini Krishnan; John G Pastorino; Evan Nevel; David Kephart; Joseph J Lee; Edward P Retzbach; Yongquan Shen; Mahnaz Fatahzadeh; Soly Baredes; Evelyne Kalyoussef; Masaru Honma; Martin E Adelson; Mika K Kaneko; Yukinari Kato; Mary Ann Young; Lisa Deluca-Rapone; Alan J Shienbaum; Kingsley Yin; Lasse D Jensen; Gary S Goldberg Journal: Oncotarget Date: 2015-04-20