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Cadherin-6 Mediates the Heterotypic Interactions between the Hemopoietic Osteoclast Cell Lineage and Stromal Cells in a Murine Model of Osteoclast Differentiation 总被引:1,自引:0,他引:1 下载免费PDF全文
Gabriel Mbalaviele Riko Nishimura Akira Myoi Maria Niewolna Sakamuri V. Reddy Di Chen Jian Feng David Roodman Gregory R. Mundy Toshiyuki Yoneda 《The Journal of cell biology》1998,141(6):1467-1476
Osteoclasts are multinucleated cells of hemopoietic origin that are responsible for bone resorption during physiological bone remodeling and in a variety of bone diseases. Osteoclast development requires direct heterotypic cell–cell interactions of the hemopoietic osteoclast precursors with the neighboring osteoblast/stromal cells. However, the molecular mechanisms underlying these heterotypic interactions are poorly understood. We isolated cadherin-6 isoform, denoted cadherin-6/2 from a cDNA library of human osteoclast-like cells. The isolated cadherin-6/2 is 3,423 bp in size consisting of an open reading frame of 2,115 bp, which encodes 705 amino acids. This isoform lacks 85 amino acids between positions 333 and 418 and contains 9 different amino acids in the extracellular domain compared with the previously described cadherin-6. The human osteoclast-like cells also expressed another isoform denoted cadherin-6/1 together with the cadherin-6. Introduction of cadherin-6/2 into L-cells that showed no cell–cell contact caused evident morphological changes accompanied with tight cell–cell association, indicating the cadherin-6/2 we isolated here is functional. Moreover, expression of dominant-negative or antisense cadherin-6/2 construct in bone marrow–derived mouse stromal ST2 cells, which express only cadherin-6/2, markedly impaired their ability to support osteoclast formation in a mouse coculture model of osteoclastogenesis. Our results suggest that cadherin-6 may be a contributory molecule to the heterotypic interactions between the hemopoietic osteoclast cell lineage and osteoblast/bone marrow stromal cells required for the osteoclast differentiation. Since both osteoclasts and osteoblasts/bone marrow stromal cells are the primary cells controlling physiological bone remodeling, expression of cadherin-6 isoforms in these two cell types of different origin suggests a critical role of these molecules in the relationship of osteoclast precursors and cells of osteoblastic lineage within the bone microenvironment. 相似文献
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Masahiro Nishikawa Akihiro Inoue Takanori Ohnishi Hajime Yano Saya Ozaki Yonehiro Kanemura Satoshi Suehiro Yoshihiro Ohtsuka Shohei Kohno Shiro Ohue Seiji Shigekawa Hideaki Watanabe Riko Kitazawa Junya Tanaka Takeharu Kunieda 《Translational oncology》2021,14(8)
The poor prognosis of glioblastoma multiforme (GBM) is primarily due to highly invasive glioma stem-like cells (GSCs) in tumors. Upon GBM recurrence, GSCs with highly invasive and highly migratory activities must assume a less-motile state and proliferate to regenerate tumor mass. Elucidating the molecular mechanism underlying this transition from a highly invasive phenotype to a less-invasive, proliferative tumor could facilitate the identification of effective molecular targets for treating GBM. Here, we demonstrate that severe hypoxia (1% O2) upregulates CD44 expression via activation of hypoxia-inducible factor (HIF-1α), inducing GSCs to assume a highly invasive tumor. In contrast, moderate hypoxia (5% O2) upregulates osteopontin expression via activation of HIF-2α. The upregulated osteopontin inhibits CD44-promoted GSC migration and invasion and stimulates GSC proliferation, inducing GSCs to assume a less-invasive, highly proliferative tumor. These data indicate that the GSC phenotype is determined by interaction between CD44 and osteopontin. The expression of both CD44 and osteopontin is regulated by differential hypoxia levels. We found that CD44 knockdown significantly inhibited GSC migration and invasion both in vitro and in vivo. Mouse brain tumors generated from CD44-knockdown GSCs exhibited diminished invasiveness, and the mice survived significantly longer than control mice. In contrast, siRNA-mediated silencing of the osteopontin gene decreased GSC proliferation. These results suggest that interaction between CD44 and osteopontin plays a key role in tumor progression in GBM; inhibition of both CD44 and osteopontin may represent an effective therapeutic approach for suppressing tumor progression, thus resulting in a better prognosis for patients with GBM. 相似文献
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Fujii M Katase N Lefeuvre M Gunduz M Buery RR Tamamura R Tsujigiwa H Nagatsuka H 《Journal of molecular histology》2011,42(6):499-504
Dickkopf (Dkk)-3, an inhibitor of the Wnt/β-catenin pathway, is reported as a potential tumor suppressor gene in many cancers.
To gain a better comprehension of the mechanisms involved in the carcinogenesis of oral squamous epithelium, protein expression
and localization of Dkk-3 and β-catenin was investigated in normal epithelium, dysplasias and squamous cell carcinoma (SCC).
An increase in β-catenin and Ki-67 expressions was observed from dysplasias to poorly differentiated SCC. Interestingly, an
increase in Dkk-3 positive cells was also noted, which was correlated to the cancer progression step. A change in Dkk-3 localization
during the transformation of normal oral epithelium to SCC was clearly observed. Dkk-3 was localized in the cell membrane
in normal oral epithelium and in dysplasias, whereas that was localized in both cell membrane and cytoplasm in SCC. These
results suggest that Dkk-3 is involved in the carcinogenesis of SCC with a distinct function from those in other cancers. 相似文献
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David McLaughlin Markus Bierling Riko Moroni Christoph Vogl Günter Schmid Simon Thiele 《Liver Transplantation》2020,10(19)
Tomographic reconstruction has been well established as a valuable tool in the analysis of polymer electrolyte fuel cell (PEMFC) electrodes. While forays have been made into applying it to polymer electrolyte water electrolyzer (PEMWE) electrodes, CO2 electrolyzer electrodes are still new ground. Here a tomographic analysis of an electrochemical CO2 reduction gas diffusion electrode by means of focused ion beam scanning electron microscope tomography is presented. The reconstruction shows a porosity of 68%. While most of the porosity is on the nanoscale, a broad tail of micropores is observed in the distribution. The spatial distribution of the pores is nonuniform. The large pores are concentrated in the center of the layer in the through‐plane direction. From the reconstruction, an effective diffusivity factor of 0.5 for the catalyst layer is calculated. The Knudsen number of 0.19 obtained from the later shows that the diffusion is mostly in the bulk regime. Flooding of the catalyst layer is likely to decrease the effective diffusivity factor substantially. 相似文献
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Toyomi Yamazaki Miki Sagisaka Riko Ikeda Toshiyuki Nakamura Noriko Matsuda Takeshi Ishii 《Bioscience, biotechnology, and biochemistry》2013,77(10):1753-1756
We purified several hundred mgs of four major theaflavins (theaflavin, theaflavin-3-O-gallate, theaflavin-3′-O-gallate, and theaflavin-3,3′-O-digallate). Among the 25 hTAS2Rs expressed in HEK293T cells, hTAS2R39 and hTAS2R14 were activated by theaflavins. Both hTAS2R39 and hTAS2R14 responded to theaflavin-3′-O-gallate. In addition, hTAS2R39 was activated by theaflavin and theaflavin-3,3′-O-gallate, but not by theaflavin-3-O-gallate. In contrast, hTAS2R14 responded to theaflavin-3-O-gallate. 相似文献
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Kazufumi Tanigawa Masashi Maekawa Takeshi Kiyoi Jun Nakayama Riko Kitazawa Sohei Kitazawa Kentaro Semba Tomohiko Taguchi Satoshi Akita Motohira Yoshida Kei Ishimaru Yuji Watanabe Shigeki Higashiyama 《Journal of cellular physiology》2019,234(10):17280-17294
Angiogenesis, the formation of new blood vessels, is involved in a variety of diseases including the tumor growth. In response to various angiogenic stimulations, a number of proteins on the surface of vascular endothelial cells are activated to coordinate cell proliferation, migration, and spreading processes to form new blood vessels. Plasma membrane localization of these angiogenic proteins, which include vascular endothelial growth factor receptors and integrins, are warranted by intracellular membrane trafficking. Here, by using a siRNA library, we screened for the sorting nexin family that regulates intracellular trafficking and identified sorting nexin 9 (SNX9) as a novel angiogenic factor in human umbilical vein endothelial cells (HUVECs). SNX9 was essential for cell spreading on the Matrigel, and tube formation that mimics in vivo angiogenesis in HUVECs. SNX9 depletion significantly delayed the recycling of integrin β1, an essential adhesion molecule for angiogenesis, and reduced the surface levels of integrin β1 in HUVECs. Clinically, we showed that SNX9 protein was highly expressed in tumor endothelial cells of human colorectal cancer tissues. High-level expression of SNX9 messenger RNA significantly correlated with poor prognosis of the patients with colorectal cancer. These results suggest that SNX9 is an angiogenic factor and provide a novel target for the development of new antiangiogenic drugs. 相似文献