TGF-β in jaw tumor fluids induces RANKL expression in stromal fibroblasts

Yamada, Chiaki; Aikawa, Tomonao; Okuno, Emi; Miyagawa, Kazuaki; Amano, Katsuhiko; Takahata, Sosuke; Kimata, Masaaki; Okura, Masaya; Iida, Seiji; Kogo, Mikihiko

doi:10.3892/ijo.2016.3548

Cited by 9 publications

(7 citation statements)

References 34 publications

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“…Genes mainly involved in coding adhesion molecules and growth factors have also been found to be upregulated in other types of CAFs, including colon (12) and pancreatic (13). The prostaglandin-endoperoxide synthase 2 gene (PTGS2), which encodes cyclooxygenase-2, was found to upregulate the expression of TGF-β2 (14). These results are consistent with another study concerning the gene expression profiling of breast CAFs, which were detected using a complementary DNA microarray (15).…”

Section: Differential Expressions Of Certain Special Genes In Cafsmentioning

confidence: 99%

Genetic alterations and epigenetic alterations of cancer-associated fibroblasts

Che

2016

Oncology Letters

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Cancer-associated fibroblasts (CAFs) are one major type of component identified in the tumor microenvironment. Studies have focused on the genetic and epigenetic status of CAFs, since they are critical in tumor progression and differ phenotypically and functionally from normal fibroblasts. The present review summarizes the recent achievements in understanding the gene profiles of CAFs and pays special attention to their possible epigenetic alterations. A total of 7 possible genetic alterations and epigenetic changes in CAFs are discussed, including gene differential expression, karyotype analysis, gene copy number variation, loss of heterozygosis, allelic imbalance, microsatellite instability, post-transcriptional control and DNA methylation. These genetic and epigenetic characteristics are hypothesized to provide a deep understanding of CAFs and a perspective on their clinical significance.

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Section: Differential Expressions Of Certain Special Genes In Cafsmentioning

confidence: 99%

Genetic alterations and epigenetic alterations of cancer-associated fibroblasts

Che

2016

Oncology Letters

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“…The tissues were then incubated with the secondary biotinylated antispecies antibody. Counterstaining was performed using hematoxylin (26).…”

Section: Generation Of Ampkα1-knockout Cell Lines With a Crispr/cas9mentioning

confidence: 99%

Metabolic reprogramming and AMPKα1 pathway activation by caulerpin in colorectal cancer cells

Zhang

Dong

et al. 2016

International Journal of Oncology

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Caulerpin, a secondary metabolite from the marine invasive green algae Caulerpa cylindracea is known to induce mitochondrial dysfunctions. In this study, the anticancer property of caulerpin was assessed in a panel of colorectal cancer cell lines. We demonstrated that caulerpin inhibited oxidative phosphorylation (OXPHOS) and facilitated an early intervention of the mitochondrial function, via inhibiting mitochondrial complex I, accompanied by the dissipation of mitochondrial membrane potential and a surge of reactive oxygen species (ROS) generation. Moreover, in response to the increment in AMP/ATP ratio, the energy sensor AMP-activated protein kinase (AMPK) was activated by caulerpin treatment in a calcium/calmodulin-dependent protein kinase 2 (CaMKK2)‑dependent manner. Distinguished effect on glycolysis was observed at different time-points after caulerpin treatment. Glycolysis was enhanced after a short time treatment with caulerpin, associated with upregulation of glucose transporter 1 (GLUT1), hexokinase II (HKII) and 6-phosphofructo-2-kinase (PFKFB3) protein expressions. However, long-term activation of AMPK by caulerpin damaged the glycolysis and glucose metabolism in colorectal cells, finally causing cell death. The persistent effect of caulerpin was mediated by AMPKα1, rather than AMPKα2, to abolish cell viability through hindering mTORC1-4E-BP1 axis. Moreover, caulerpin synergized with the glycolytic inhibitor 3BP in inhibiting cellular proliferation both in vitro and in vivo. Our findings on the previously uncharacterized anticancer effects of caulerpin may provide potential therapeutic approaches targeting the colorectal carcinoma metabolism.

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“…Moreover, there is evidence to indicate that the cyst fluid level of interleukin (IL)-1α in OKCs is significantly higher than that in DC or RC fluids, associated with a higher expression level of matrix metalloproteinase-9 (MMP9) in the OKC epithelium ( 27 , 28 ). In addition, the higher level of transforming growth factor-β (TGF-β) within the fluids plays a significant role in inducing RANKL expression in the stroma, which is essential for the osteoclastogenesis of OKCs ( 29 ). These data suggest that different components within the cyst fluids may contribute to the development of OKCs.…”

Section: Discussionmentioning

confidence: 99%

Increased level of cell-derived microparticles in the cyst fluids of odontogenic keratocysts

et al. 2018

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The aim of this study was to examine the level and basic characteristics of cell-derived microparticles (MPs) in the cyst fluids of odontogenic keratocysts (OKCs). For this purpose, MPs from the cyst fluids (CFMPs) of OKCs were purified by a classic differential centrifugation method and characterized by a transmission electron microscope and fluorescence microscope. Flow cytometric analysis was used to determine the size, concentration and cellular origins of the CFMPs. Moreover, the expression level of receptor activator for nuclear factor-κB ligand in the OKCs was evaluated by immunohistochemical staining and then analyzed for its correlation with the concentration of CFMPs by Spearman's rank correlation test. In addition, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and tartaric-resistant acid phosphatase (TRAP) staining were performed to examine the osteoclastogenesis of mouse bone marrow-derived macrophages (BMMs) in response to CFMPs. The results revealed that the levels of total CFMPs were significantly elevated in OKCs compared with dentigerous cysts (DCs) and radicular cysts (RCs). In addition, in vitro experiments further revealed that CFMPs derived from the OKCs of patients could be taken up by BMMs, leading to a significant increase in the mRNA expression levels of nuclear factor of activated T-cells 1 (NFATc1) and TRAP. Moreover, TRAP-positive multinucleated osteoclasts were successfully cultured in the presence of macrophage colony-stimulating factor (M-CSF) and CFMPs with BMMs. On the whole, our findings indicate that patients with OKCs have higher levels of CFMPs compared with patients with DCs and RCs, which may be associated with the bone resorption of OKCs.

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TGF-β in jaw tumor fluids induces RANKL expression in stromal fibroblasts

Cited by 9 publications

References 34 publications

Genetic alterations and epigenetic alterations of cancer-associated fibroblasts

Genetic alterations and epigenetic alterations of cancer-associated fibroblasts

Metabolic reprogramming and AMPKα1 pathway activation by caulerpin in colorectal cancer cells

Increased level of cell-derived microparticles in the cyst fluids of odontogenic keratocysts

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