Immunostaining for peroxisome proliferator gamma distinguishes dedifferentiated liposarcoma from other retroperitoneal sarcomas

Horvai, Andrew E.; Schaefer, Jochen T.; Nakakura, Eric K.; O’Donnell, Richard J.

doi:10.1038/modpathol.3801017

Cited by 21 publications

(13 citation statements)

References 31 publications

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“…Furthermore, Oil Red O staining of cryosections revealed the presence of lipid droplets in the tumors. Therefore, tumors derived from miPS-LLCev cells are probably liposarcoma 28, 29. Additionally, during tumor development, we observed some animals with abdominal bleeding, were bearing disseminated tumor nodules in the mesentery (Additional File 1: Supplementary Fig.…”

Section: Resultsmentioning

confidence: 97%

Characterization of Cancer Stem-Like Cells Derived from Mouse Induced Pluripotent Stem Cells Transformed by Tumor-Derived Extracellular Vesicles

Yan¹,

Mizutani²,

Chen³

et al. 2014

J. Cancer

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Several studies have shown that cancer niche can perform an active role in the regulation of tumor cell maintenance and progression through extracellular vesicles-based intercellular communication. However, it has not been reported whether this vesicle-mediated communication affects the malignant transformation of normal stem cells/progenitors. We have previously reported that the conditioned medium derived from the mouse Lewis Lung Carcinoma (LLC) cell line can convert mouse induced pluripotent stem cells (miPSCs) into cancer stem cells (CSCs), indicating that normal stem cells when placed in an aberrant microenvironment can give rise to functionally active CSCs. Here, we focused on the contribution of tumor-derived extracellular vesicles (tEVs) that are secreted from LLC cells to induce the transformation of miPSCs into CSCs. We isolated tEVs from the conditioned medium of LLC cells, and then the differentiating miPSCs were exposed to tEVs for 4 weeks. The resultant tEV treated cells (miPS-LLCev) expressed Nanog and Oct3/4 proteins comparable to miPSCs. The frequency of sphere formation of the miPS-LLCev cells in suspension culture indicated that the self-renewal capacity of the miPS-LLCev cells was significant. When the miPS-LLCev cells were subcutaneously transplanted into Balb/c nude mice, malignant liposarcomas with extensive angiogenesis developed. miPS-LLCevPT and miPS-LLCevDT, the cells established from primary site and disseminated liposarcomas, respectively, showed their capacities to self-renew and differentiate into adipocytes and endothelial cells. Moreover, we confirmed the secondary liposarcoma development when these cells were transplanted. Taken together, these results indicate that miPS-LLCev cells possess CSC properties. Thus, our current study provides the first evidence that tEVs have the potential to induce CSC properties in normal tissue stem cells/progenitors.

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Section: Resultsmentioning

confidence: 97%

Characterization of Cancer Stem-Like Cells Derived from Mouse Induced Pluripotent Stem Cells Transformed by Tumor-Derived Extracellular Vesicles

Yan¹,

Mizutani²,

Chen³

et al. 2014

J. Cancer

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“…Rarely, S100 protein immunoreactivity is used to identify adipocytic cells and lipoblasts in liposarcomas 2. Recently, peroxisome proliferator-activated receptor γ, a nuclear receptor that regulates growth and differentiation of adipocytes, was shown to stain lipogenic and non-lipogenic areas of DDLPS 22. In this study, the expression of MDM2 and CDK4 was examined by IHC in a series of soft tissue tumours.…”

Section: Discussionmentioning

confidence: 98%

Can MDM2 and CDK4 make the diagnosis of well differentiated/dedifferentiated liposarcoma? An immunohistochemical study on 129 soft tissue tumours

et al. 2009

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“…The clinical and pathological findings of 25 tumors were reported previously. 24 The most common presentation was a retroperitoneal mass (n ¼ 21, 72%) with the remaining cases distributed between the extremity, trunk, abdomen and spermatic cord. In 25 cases (86%), the dedifferentiated liposarcoma was present at the time of first diagnosis (synchronous), whereas in the remaining cases (n ¼ 4, 14%), a diagnosis of well-differentiated liposarcoma preceded the presentation of the dedifferentiated liposarcoma by 1-5 years (metachronous).…”

Section: Clinicopathologic Characteristicsmentioning

confidence: 99%

“…We recently reported more detailed clinicopathologic parameters of 25 of these cases. 24 The diagnosis was based on light microscopic, radiographic and clinical features. The 'gold standard' of diagnosis in every case was the presence of a well-differentiated liposarcoma either adjacent to macroscopic areas of sarcoma without lipogenic differentiation (synchronous) or previously removed from the same anatomical site (metachronous).…”

Section: Case Selectionmentioning

confidence: 99%

Similarity in genetic alterations between paired well-differentiated and dedifferentiated components of dedifferentiated liposarcoma

et al. 2009

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Liposarcoma represents a unique model insofar as some well-differentiated liposarcomas progress to nonlipogenic, so-called 'dedifferentiated,' forms. The well-differentiated and dedifferentiated family of liposarcomas demonstrates amplification of the chromosome subregion 12q13-q15 with resultant amplification of the MDM2 and CDK4 genes. However, the specific genetic changes that distinguish between well-differentiated and dedifferentiated liposarcomas are less well understood. To study the genetic changes in dedifferentiated liposarcomas, paired well-differentiated and dedifferentiated components of 29 tumors were analyzed separately by array-based comparative genomic hybridization. A bacterial artificial chromosome array at B1-Mb resolution was used. The genetic changes were compared with clinical presentation, grade of the dedifferentiated component and overexpression of MDM2 and CDK4. Most tumors (n ¼ 21, 72%) were retroperitoneal, with both components present at initial diagnosis (n ¼ 25, 86%). Eight tumors (28%) were classified as low-grade dedifferentiation. In four cases (14%), a well-differentiated liposarcoma preceded the presentation of the dedifferentiated tumor by 1-5 years. 12q13-q15 was amplified in all tumors. Using unsupervised hierarchical clustering of copy-number changes, all but two tumors showed close similarities between well-differentiated and dedifferentiated components, and segregated as pairs. Dedifferentiated components had more total amplifications (P ¼ 0.008) and a trend for gain at 19q13.2, but no genetic changes were significant in distinguishing between the two components. High-level amplifications of 1p21-32 (n ¼ 7, 24%), 1q21-23 (n ¼ 9, 31%), 6q23-24 (n ¼ 6, 21%) and 12q24 (n ¼ 3, 10%) were common, but none significantly correlated with differentiation. Presentation and grade correlated with the frequency of changes at a number of genetic loci (Po0.001), whereas CDK4 immunostaining showed negative correlation with 12q13.13 amplification. The genotypic similarity, at the limit of the array's resolution, between components implies that most genetic changes precede phenotypic 'progression,' early in tumorigenesis. The relationship between genetic changes and presentation or grade may reflect differences in factors that control genomic instability or the background genotype of the tumor.

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Immunostaining for peroxisome proliferator gamma distinguishes dedifferentiated liposarcoma from other retroperitoneal sarcomas

Cited by 21 publications

References 31 publications

Characterization of Cancer Stem-Like Cells Derived from Mouse Induced Pluripotent Stem Cells Transformed by Tumor-Derived Extracellular Vesicles

Characterization of Cancer Stem-Like Cells Derived from Mouse Induced Pluripotent Stem Cells Transformed by Tumor-Derived Extracellular Vesicles

Can MDM2 and CDK4 make the diagnosis of well differentiated/dedifferentiated liposarcoma? An immunohistochemical study on 129 soft tissue tumours

Similarity in genetic alterations between paired well-differentiated and dedifferentiated components of dedifferentiated liposarcoma

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