Expression of E-cadherin in chordomas: diagnostic marker and possible role of tumor cell affinity

Mori, Kanji; Chano, Tokuhiro; Kushima, Ryoji; Hukuda, Sinsuke; Okabe, Hidetoshi

doi:10.1007/s004280100525

Cited by 19 publications

(15 citation statements)

References 11 publications

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“…As shown in Figure 1A-1C, ET-1 induced wound healing (Figure 1A), migration (Figure 1B) and invasion (Figure 1C) of chondrosarcoma cells in a dose-dependent manner. The essential features of EMT in the context of tumor progression are enhanced cell migration and invasion [17, 18]. To examine whether ET-1 is required for EMT in chondrosarcoma, the chondrosarcoma cell lines were treated with ET-1.…”

Section: Resultsmentioning

confidence: 99%

Endothelin-1 promotes epithelial-mesenchymal transition in human chondrosarcoma cells by repressing miR-300

Huang

Hsieh

et al. 2016

Oncotarget

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Chondrosarcoma is a malignant tumor of mesenchymal origin predominantly composed of cartilage-producing cells. This type of bone cancer is extremely resistant to radiotherapy and chemotherapy. Surgical resection is the primary treatment, but is often difficult and not always practical for metastatic disease, so more effective treatments are needed. In particular, it would be helpful to identify molecular markers as targets for therapeutic intervention. Endothelin-1 (ET-1), a potent vasoconstrictor, has been shown to enhance chondrosarcoma angiogenesis and metastasis. We report that ET-1 promotes epithelial–mesenchymal transition (EMT) in human chondrosarcoma cells. EMT is a key pathological event in cancer progression, during which epithelial cells lose their junctions and apical-basal polarity and adopt an invasive phenotype. Our study verifies that ET-1 induces the EMT phenotype in chondrosarcoma cells via the AMP-activated protein kinase (AMPK) pathway. In addition, we show that ET-1 increases EMT by repressing miR-300, which plays an important role in EMT-enhanced tumor metastasis. We also show that miR-300 directly targets Twist, which in turn results in a negative regulation of EMT. We found a highly positive correlation between ET-1 and Twist expression levels as well as tumor stage in chondrosarcoma patient specimens. Therefore, ET-1 may represent a potential novel molecular therapeutic target in chondrosarcoma metastasis.

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Section: Resultsmentioning

confidence: 99%

Endothelin-1 promotes epithelial-mesenchymal transition in human chondrosarcoma cells by repressing miR-300

Huang

Hsieh

et al. 2016

Oncotarget

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“…While not a specific aim of this study, the identification of these positive and negative notochordal markers may also be helpful to understand the biology of chordomas …”

Section: Discussionmentioning

confidence: 99%

Spatiotemporal analysis of putative notochordal cell markers reveals CD24 and keratins 8, 18, and 19 as notochord‐specific markers during early human intervertebral disc development

Rodrigues-Pinto

Berry

Hanley

et al. 2016

Journal Orthopaedic Research

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In humans, the nucleus pulposus (NP) is composed of large vacuolated notochordal cells in the fetus but, soon after birth, becomes populated by smaller, chondrocyte‐like cells. Although animal studies indicate that notochord‐derived cells persist in the adult NP, the ontogeny of the adult human NP cell population is still unclear. As such, identification of unique notochordal markers is required. This study was conducted to determine the spatiotemporal expression of putative human notochordal markers to aid in the elucidation of the ontogeny of adult human NP cells. Human embryos and fetuses (3.5–18 weeks post‐conception (WPC)) were microdissected to isolate the spine anlagens (notochord and somites/sclerotome). Morphology of the developing IVD was assessed using hematoxylin and eosin. Expression of keratin (KRT) 8, KRT18, KRT19, CD24, GAL3, CD55, BASP1, CTGF, T, CD90, Tie2, and E‐cadherin was assessed using immunohistochemistry. KRT8, KRT18, KRT19 were uniquely expressed by notochordal cells at all spine levels at all stages studied; CD24 was expressed at all stages except 3.5 WPC. While GAL3, CD55, BASP1, CTGF, and T were expressed by notochordal cells at specific stages, they were also co‐expressed by sclerotomal cells. CD90, Tie2, and E‐cadherin expression was not detectable in developing human spine cells at any stage. This study has identified, for the first time, the consistent expression of KRT8, KRT18, KRT19, and CD24 as human notochord‐specific markers during early IVD development. Thus, we propose that these markers can be used to help ascertain the ontogeny of adult human NP cells. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. J Orthop Res 34:1327–1340, 2016.

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“…The same study showed that the expression of E-cadherin was decreased and correlated with increased mortality. These findings suggest that the cadherins play a crucial role in the malignancy of chordomas [41,60,65,66,104].…”

Section: Invasion and Metastasismentioning

confidence: 99%

The molecular aspects of chordoma

et al. 2015

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Chordomas are one of the rarest bone tumors, and they originate from remnants of embryonic notochord along the spine, more frequently at the skull base and sacrum. Although they are relatively slow growing and low grade, chordomas are highly recurrent, aggressive, locally invasive, and prone to metastasize to the lungs, bone, and the liver. Chordomas highly and generally show a dual epithelial-mesenchymal differentiation. These tumors resist chemotherapy and radiotherapy; therefore, radical surgery and high-dose radiation are the most used treatments, although there is no standard way to treat the disease. The molecular biology process behind the initiation and progression of a chordoma needs to be revealed for a better understanding of the disease and to develop more effective therapies. Efforts to discover the mysteries of these molecular aspects have delineated several molecular and genetic alterations in this tumor. Here, we review and describe the emerging insights into the molecular landscape of chordomas.

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Expression of E-cadherin in chordomas: diagnostic marker and possible role of tumor cell affinity

Cited by 19 publications

References 11 publications

Endothelin-1 promotes epithelial-mesenchymal transition in human chondrosarcoma cells by repressing miR-300

Endothelin-1 promotes epithelial-mesenchymal transition in human chondrosarcoma cells by repressing miR-300

Spatiotemporal analysis of putative notochordal cell markers reveals CD24 and keratins 8, 18, and 19 as notochord‐specific markers during early human intervertebral disc development

The molecular aspects of chordoma

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