Type X collagen expression and hypertrophic differentiation in chondrogenic neoplasias

Aigner, Thomas; Frischholz, Svenja; Dertinger, Susanne; Beier, Frank; Girkontaitė, Irutė; K, von der Mark

doi:10.1007/s004180050130

Cited by 33 publications

(38 citation statements)

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“…Myxoid areas of conventional chondrosarcomas strongly express aggrecan 34,43 and, at least focally, collagen types II and X, features not seen in extraskeletal myxoid chondrosarcoma. 24,34 The difference between these two types of neoplasms is also evident at the genetic level. Myxoid variants of skeletal chondrosarcomas do not show the chromosomal translocations found typically in extraskeletal myxoid chondrosarcomas.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, the relationship between extraskeletal and skeletal myxoid chondrosarcoma is unclear, 3 and molecular and ultrastructural evidence suggests both being completely different tumor entities. 3,18 Chondrogenic differentiation in fetal development, 20,21 in adult secondary chondrogenesis, 22 and in chondrogenic neoplasms [23][24][25][26] can be identified and monitored by investigating marker genes of chondrocytic differentiation such as collagen subtypes. In particular, collagen types II and X are distinct markers for the chondrocytic cell lineage (for a review see Cancedda et al 27 ).…”

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confidence: 99%

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Extraskeletal myxoid chondrosarcomas do not show a chondrocytic phenotype

2004

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Extraskeletal myxoid chondrosarcoma is a rare mesenchymal soft-tissue malignancy of putative chondrocytic differentiation. Occasional overt cartilage formation, positivity for S-100 protein, and ultrastructural analysis have supported this view. However, most extraskeletal myxoid chondrosarcomas do not show chondroid tissue formation, and S-100 protein is found much less commonly than has been reported. Both these observations cast doubt on the histogenetic classification of extraskeletal myxoid chondrosarcoma as a chondroblastic entity. Mostly using matrix proteins as markers of mesenchymal cell differentiation, we investigated the biochemical matrix composition and cellular phenotype of the tumor cells in representative specimens from 14 extraskeletal myxoid chondrosarcomas. In all but one tumor specimen, which showed histomorphologically overt cartilage formation, only occasional staining for the proteoglycan aggrecan was found. Specimens from two tumors showed presence of collagen type II, and none was positive for collagen type X. Instead, collagen types I, III, and VI were diffusely positive. Also, S-100 protein was largely absent. Our results suggest that the basic cellular phenotype of extraskeletal myxoid chondrosarcoma is not chondrocytic or prechondrocytic and that extraskeletal myxoid chondrosarcoma is not a chondrosarcomatous entity. Extraskeletal myxoid chondrosarcoma consists most likely of primitive mesenchymal cells with focal, multidirectional differentiation. Chondrocytic differentiation is an unusual facet in the spectrum of differentiation patterns exhibited by these lesions.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Extraskeletal myxoid chondrosarcomas do not show a chondrocytic phenotype

2004

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“…24 Immunohistochemistry was performed for proliferation rate analysis using a monoclonal antibody against Ki-67 (clone MIB1, 1:100; Dako, Glostrup, Germany) according to standard laboratory procedures. 25 …”

Section: Histopathological and Immunohistochemistry Evaluationmentioning

confidence: 99%

Primary cilia organization reflects polarity in the growth plate and implies loss of polarity and mosaicism in osteochondroma

Andrea

Wiweger

Prins

et al. 2010

Laboratory Investigation

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Primary cilia are specialized cell surface projections found on most cell types. Involved in several signaling pathways, primary cilia have been reported to modulate cell and tissue organization. Although they have been implicated in regulating cartilage and bone growth, little is known about the organization of primary cilia in the growth plate cartilage and osteochondroma. Osteochondromas are bone tumors formed along the growth plate, and they are caused by mutations in EXT1 or EXT2 genes. In this study, we show the organization of primary cilia within and between the zones of the growth plate and osteochondroma. Using confocal and electron microscopy, we found that in both tissues, primary cilia have a similar formation but a distinct organization. The shortest ciliary length is associated with the proliferative state of the cells, as confirmed by Ki-67 immunostaining. Primary cilia organization in the growth plate showed that nonpolarized chondrocytes (resting zone) are becoming polarized (proliferating and hypertrophic zones), orienting the primary cilia parallel to the longitudinal axis of the bone. The alignment of primary cilia forms one virtual axis that crosses the center of the columns of chondrocytes reflecting the polarity axis of the growth plate. We also show that primary cilia in osteochondromas are found randomly located on the cell surface. Strikingly, the growth plate-like polarity was retained in sub-populations of osteochondroma cells that were organized into small columns. Based on this, we propose the existence of a mixture ('mosaic') of normal lining (EXT þ /À or EXT wt/wt ) and EXT À/À cells in the cartilaginous cap of osteochondromas.

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“…Histochemical and immunohistochemical analyses have shown that chondrosarcomas showing mainly mature and terminally differentiated (hypertrophic) chondrocytic phenotypes display only scant proliferation, whereas less differentiated chondrosarcomas with the phenotype of dedifferentiated chondrocytes show significantly higher proliferative activity (4). These features are highly correlated with prognosis (5). These findings suggest the possibility that the induction of differentiation in chondrosarcoma cells could lead to a novel therapeutic strategy.…”

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The Effects of Histone Deacetylase Inhibitors on the Induction of Differentiation in Chondrosarcoma Cells

Sakimura

Tanaka

Yamamoto

et al. 2007

Clinical Cancer Research

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Purpose: Histologically, chondrosarcomas represent the degree of chondrogenic differentiation, which is associated with the prognosis of the disease. Histone acetylation and deacetylation play key roles in the regulation of chondrocytic differentiation. Here, we describe the antitumor effects of histone deacetylase (HDAC) inhibitors as differentiating reagents on chondrosarcomas. Experimental Design: We examined the effects of a HDAC inhibitor, depsipeptide, on the growth of chondrosarcoma cell lines.We also investigated the modulation of the expression levels of extracellular matrix genes and the induction of phenotypic change in chondrosarcoma cells treated with depsipeptide. Finally, we examined the antitumor effect of depsipeptide on chondrosarcoma in vivo. Results: Depsipeptide inhibited the growth of chondrosarcoma cells by inducing cell cycle arrest and/or apoptosis. HDAC inhibitors increased the expression of the a1 chain of type II collagen (COL2A1) gene due to the enhanced histone acetylation in the promoter and enhancer. Depsipeptide also up-regulated the expressions of aggrecan and the a2 chain of type XI collagen (COL11A2) mRNA in a dose-dependent manner. Moreover, long-term treatment with a low dose of depsipeptide resulted in the induction of differentiation into hypertrophic phenotype, as shown by the increment of the a1 chain of type X collagen (COL10A1) expression in chondrosarcoma cells. In vivo studies and histologic analyses confirmed that depsipeptide significantly inhibited tumor growth and induced differentiation into the hypertrophic and mineralized state in chondrosarcoma cells. Conclusions:These results strongly suggest that HDAC inhibitors may be promising reagents for use as a differentiating chemotherapy against chondrosarcomas.Chondrosarcomas represent the second most prevalent primary skeletal malignancy. Because chondrosarcomas are highly resistant to conventional chemotherapy and radiotherapy, surgery is the only effective form of treatment. To date, no effective adjuvant therapy exists for inoperable chondrosarcomas (1, 2). Thus, a novel approach to therapeutic strategy is a priority for improving the prognosis as related to local recurrence, metastasis, and survival.A recent study has shown that the cartilaginous cells of the growth plate during their different states of differentiation and the distinct histologic chondrosarcoma subtypes show striking histologic similarities (3). The normal growth plate represents the chondrocytic maturation process including resting, proliferative, prehypertrophic, and hypertrophic chondrocytes. As a final step, the cartilage matrix becomes mineralized and hypertrophic cells undergo apoptosis. The process is accompanied by the sequential gene expression pattern of the characteristic extracellular matrix. After commitment to the chondrocyte lineage, mesenchymal cells undergo condensation, cease to express type I collagen (COL1), and then differentiate into a chondrocytic phenotype characterized by the expression of type II, IX, and XI...

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Type X collagen expression and hypertrophic differentiation in chondrogenic neoplasias

Cited by 33 publications

References 33 publications

Extraskeletal myxoid chondrosarcomas do not show a chondrocytic phenotype

Extraskeletal myxoid chondrosarcomas do not show a chondrocytic phenotype

Primary cilia organization reflects polarity in the growth plate and implies loss of polarity and mosaicism in osteochondroma

The Effects of Histone Deacetylase Inhibitors on the Induction of Differentiation in Chondrosarcoma Cells

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