Molecular pathways involved in crosstalk between cancer cells, osteoblasts and osteoclasts in the invasion of bone by oral squamous cell carcinoma

Quan, Jingjing; Zhou, Chuan‐Xiang; Johnson, Newell W.; Francis, Glenn; Dahlstrom, Jane E.; Gao, Jin

doi:10.1097/pat.0b013e3283513f3b

Cited by 24 publications

(22 citation statements)

References 39 publications

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“…Human foetal osteoblasts (hFOB) were obtained from American Type Tissue Collection (ATCC, Rockville, USA), and grown in DMEM/F12 with 10 % FBS plus 300 μg/mL geneticin (G418) at 34 °C in an incubator. CM [17] was collected from OSCC cell lines SCC15 and SCC25, and from hFOB, and used for indirect co-culture: OSCC cells were treated with CM of hFOB cells for 48hs. To block the endogenous TGF-β1 secreted by hFOB cells, TGF-β inhibitor (SB431542, 188 nM, Sigma) was used in CM of hFOB to treat OSCC cells for 48 h. To examine the effects of TGF-β1 on OSCC cells, equal numbers of SCC25, HN5 and Tca8113 cells were plated in serum-free medium, starved for 12 h, and then treated with TGF-β1 (5 ng/mL) for 0, 1–3 days.…”

Section: Methodsmentioning

confidence: 99%

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Transforming growth factor-β1 treatment of oral cancer induces epithelial-mesenchymal transition and promotes bone invasion via enhanced activity of osteoclasts

Quan

Elhousiny

Johnson

et al. 2013

Clin Exp Metastasis

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This study investigates relationships between EMT and bone invasion by OSCC. Three OSCC cell lines, SCC25, HN5, and Tca8113 were artificially induced to display EMT by adding 5 ng/mL of TGF-β1 to culture media for 1–3 days. Cell morphology and phenotypic changes was examined by immunocytochemical staining of CK and VIM. EMT markers, cell-invasion factors, and osteoclast-related molecules were analysed at mRNA, gelatine and protein levels by real-time PCR, gelatine zymography and Western blotting respectively. Mature osteoclasts differentiated from Raw264.7 cells were treated by conditioned medium (CM) of OSCC cells with/without TGF-β1. Immunohistochemistry was performed to validate proteins of CK, VIM, E-cad and Snail1 in OSCC tissue samples with bone invasion. Results showed minimal staining of VIM was found in SCC25 and HN5, while Tca8113 cells stained strongly. EMT markers Twist1 and N-cad were up-regulated; Snail1 and E-cad down-regulated in all cells. Of factors associated with invasion, MMP-2 was unchanged and MMP-9 increased in SCC25 and Tca8113, while MMP-2 was increased and MMP-9 unchanged in HN5. For osteoclast-related molecules, both MT1-MMP and RANKL were up-regulated, while OPG was down-regulated in all cells. CM of OSCC cells pre-treated with TGF-β1 showed to prolong survival of osteoclasts up to 4 days. All target molecules were validated in OSCC samples of bone invasion. These findings suggest that TGF-β1 not only induces EMT to increase the capacity of OSCC for invasion, but also promotes factors which prolong osteoclast survival. TGF-β1 may enhance the ability of MMP2/9 in resorbing bone and favouring invasion of cancer cells.

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Section: Methodsmentioning

confidence: 99%

“…In the present study, we found that conditioned medium (CM) of osteoblasts induced gene expression level changes of OSCC cells [17], for example, Twist1, was up-regulated in these cells after such treatment. The expression of MMP-2 protein level was increased, while MMP-9 was decreased.…”

Section: Introductionmentioning

confidence: 99%

Transforming growth factor-β1 treatment of oral cancer induces epithelial-mesenchymal transition and promotes bone invasion via enhanced activity of osteoclasts

Quan

Elhousiny

Johnson

et al. 2013

Clin Exp Metastasis

Self Cite

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“…Recently, it was demonstrated that the functions of OB and OC showed correlative dependence (Choi et al, 2012;Yamashita et al, 2012). OB could regulate OC maturation and activation by secreting interleukin and other cytokines (Quan et al, 2012). However, the mechanism is still unclear.…”

Section: Discussionmentioning

confidence: 99%

IL-23 promotes osteoclastogenesis in osteoblast-osteoclast co-culture system

Kang¹,

Zhang²

2014

Genet. Mol. Res.

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ABSTRACT. The aim of this study was to determine the effect of IL-23 on the activity and proliferation of osteoclasts (OC) in co-culture with osteoblasts (OB). OB and OC were individually separated from the skull and femoral bone of a SD rat. OB-OC co-culture with IL-23 added was designed as the experimental group, while the OB-OC co-culture without IL-23 was the control group. In the experimental group, five different concentrations of IL-23 were added, and the cells were then cultured for 24, 48 and 72 h. For each concentration at these three time points, cell proliferation, tartrate-resistant acid phosphatase (TRAP) activity and the lacunae in the bone slices were evaluated, compared with control group at the same time points. Compared to the control group, proliferation and TRAP activity of OC were significantly increased at 24, 48 and 72 h with addition of 0.5 to 10 ng/mL IL-23 (P < 0.05). In addition, a dose-and time-dependent correlation between the effect of IL-23 and osteoclastogenesis was noticed though the comparison. Moreover, the area of lacunar resorption in each experimental group was significantly larger than in the control group (P

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“…Inicialmente, as células tumorais secretam proteases, que são enzimas capazes de degradar componentes da matriz extracelular, facilitando a invasão do tumor pelos tecidos. As proteases também atuam na diferenciação das células ósseas, recrutando osteoclastos que passam a reabsorver a matriz mineralizada do osso (26,27…”

Section: Mecanismos Moleculares Da Invasão óSseaunclassified

“…As MMPs são uma parte essencial do equilíbrio do processo de formação/reabsorção óssea em condições normais, mas também são expressas pelas células tumorais (33). No câncer, as MMPs contribuem para a migração celular e também tem uma participação essencial na diferenciação e maturação das células ósseas (26,27).…”

Section: Mmpsunclassified

Estudo das proteínas da transição epitélio-mesênquima na invasão óssea do carcinoma epidermóide da cavidade oral

Vanini¹

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Vanini J.V. Study of epithelial-mesenchymal proteins in bone invasion of oral squamous cell carcinoma [dissertation]. São Paulo: Universidade de São Paulo, Faculdade de Odontologia; 2019. Original version. Squamous cell carcinoma is the most common cancer of the oral cavity. When the tumor invades the bone tissue, the prognostic and survival rate decreases a lot, and the treatment becomes more aggressive, with several damages to the patient and health system. Many of the molecular mechanisms of this process are not understood yet, but it's already known that one of central processes of tumor evolution -adjacent tissues invasion and metastasis -is a large spectrum of phenotypic changes in epithelial cells to mesenchymal, in a process named as epithelial-mesenchymal transition. During this phenomenon, there are a lot of changes in the cells protein expression, which can be used as biomarkers for diagnostic and determination of tumor aggressiveness in early stages, as also the possibility of developing new treatment drugs, more specific and efficient. The objective of this retrospective study is to evaluate if epithelial-mesenchymal transition is present in bone invasion of oral squamous cell carcinoma, by immunohistochemistry evaluation of E-cadherin, Twist, Vimentin, TGFβ1 and Periostin expression. The proteins expression was very heterogeneous. E-cadherinand Twist showed high levels of positivity, and were found associations between Twist positive expression and infiltrative bone invasion pattern (p=0,041), primary tumor site close to bone (p=0,014) and Periostin negative expression (p=0,031), suggesting this transcription factor could be strongly involved in the disease evolution in bone tissue. There are also associations between Vimentin expression and tumor size. The results of this study suggests that epithelial-mesenchymal transition could be present in some level of its spectrum in bone invasion of oral squamous cell carcinoma.

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Molecular pathways involved in crosstalk between cancer cells, osteoblasts and osteoclasts in the invasion of bone by oral squamous cell carcinoma

Cited by 24 publications

References 39 publications

Transforming growth factor-β1 treatment of oral cancer induces epithelial-mesenchymal transition and promotes bone invasion via enhanced activity of osteoclasts

Transforming growth factor-β1 treatment of oral cancer induces epithelial-mesenchymal transition and promotes bone invasion via enhanced activity of osteoclasts

IL-23 promotes osteoclastogenesis in osteoblast-osteoclast co-culture system

Estudo das proteínas da transição epitélio-mesênquima na invasão óssea do carcinoma epidermóide da cavidade oral

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