scholarly journals Separation of cell survival, growth, migration, and mesenchymal transdifferentiation effects of fibroblast secretome on tumor cells of head and neck squamous cell carcinoma

Tumor Biology ◽  
2017 ◽  
Vol 39 (11) ◽  
pp. 101042831770550 ◽  
Author(s):  
Veronika Maria Metzler ◽  
Christian Pritz ◽  
Anna Riml ◽  
Angela Romani ◽  
Raphaela Tuertscher ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Tumor Cell ◽  
Cell Survival ◽  
Tumor Cells ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Paracrine Factors ◽  
Mesenchymal Transition ◽  
Growth Factor Beta

Fibroblasts play a central role in tumor invasion, recurrence, and metastasis in head and neck squamous cell carcinoma. The aim of this study was to investigate the influence of tumor cell self-produced factors and paracrine fibroblast–secreted factors in comparison to indirect co-culture on cancer cell survival, growth, migration, and epithelial–mesenchymal transition using the cell lines SCC-25 and human gingival fibroblasts. Thereby, we particularly focused on the participation of the fibroblast-secreted transforming growth factor beta-1.Tumor cell self-produced factors were sufficient to ensure tumor cell survival and basic cell growth, but fibroblast-secreted paracrine factors significantly increased cell proliferation, migration, and epithelial–mesenchymal transition–related phenotype changes in tumor cells. Transforming growth factor beta-1 generated individually migrating disseminating tumor cell groups or single cells separated from the tumor cell nest, which were characterized by reduced E-cadherin expression. At the same time, transforming growth factor beta-1 inhibited tumor cell proliferation under serum-starved conditions. Neutralizing transforming growth factor beta antibody reduced the cell migration support of fibroblast-conditioned medium. Transforming growth factor beta-1 as a single factor was sufficient for generation of disseminating tumor cells from epithelial tumor cell nests, while other fibroblast paracrine factors supported tumor nest outgrowth. Different fibroblast-released factors might support tumor cell proliferation and invasion, as two separate effects.

Intestinal transformation results in transforming growth factor-beta-dependent alteration in tumor cell-cell matrix interactions

Surgery ◽  
2003 ◽  
Vol 133 (5) ◽  
pp. 568-579 ◽  
Author(s):  
David H. Berger ◽  
Christine A. O'Mahony ◽  
Hongmiao Sheng ◽  
Jinyi Shao ◽  
Daniel Albo ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tumor Cell ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Growth Factor Beta ◽  
Cell Matrix Interactions ◽  
Cell Cell

Dysregulated miR-142, -33b and -423 in granulosa cells target TGFBR1 and SMAD7: a possible role in polycystic ovary syndrome

2019 ◽  
Vol 25 (10) ◽  
pp. 638-646 ◽  
Author(s):  
Yan Li ◽  
Yungai Xiang ◽  
Yuxia Song ◽  
Lijing Wan ◽  
Guo Yu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Polycystic Ovary Syndrome ◽  
Granulosa Cells ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Growth Factor Beta ◽  
Tgfb Signaling

Abstract It is well established that microRNA (miRNA) expression profiles are altered in patients with polycystic ovary syndrome (PCOS). In addition, abnormal transforming growth factor beta (TGFB) signaling in granulosa cells is related to the pathological conditions of PCOS. However, the function of dysregulated miRNAs in PCOS is still unclear. In this study, we aimed to elucidate the roles of specific miRNAs in PCOS. We collected follicular fluid from 46 patients with PCOS and 32 healthy controls. Granulosa cells (GCs) were separated and the levels of six candidate miRNAs were determined by quantitative RT-PCR. The direct targets of three dysregulated miRNAs were predicted using bioinformatic tools and confirmed using a dual luciferase assay and immunoblotting. The biological function of three dysregulated miRNAs in primary GCs was determined using a cell proliferation assay and flow cytometry. We found that miR-423 expression was downregulated (P = 0.038), and the levels of miR-33b (P = 0.032) and miR-142 (P = 0.021) were upregulated in GCs from patients with PCOS, compared to controls. miR-423 directly repressed SMAD family member 7 (SMAD7) expression, while transforming growth factor beta receptor 1 (TGFBR1) was a direct target of both miR-33b and miR-142. An RNA oligonucleotide mixture containing miR-423 inhibitor, miR-33b mimic, and miR-142 mimic repressed TGFB signaling, promoted cell proliferation (P = 0.0098), repressed apoptosis (P = 0.027), and increased S phase cell numbers (P = 0.0036) in primary cultures of GCs, compared to the cells treated with a sequence scrambled control RNA oligonucleotide. This study unveiled the possible roles of three miRNAs in PCOS and might provide candidate biomarkers for PCOS diagnosis while in vivo functional studies, using transgenic or knockout mouse models, are expected to confirm the roles of dysregulated miRNAs in the pathogenesis of PCOS.

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