Human osteosarcoma expresses specific ephrin profiles

Varelias, Antiopi; Koblar, Simon; Cowled, Prue; Carter, Christopher D.; Clayer, Mark

doi:10.1002/cncr.10749

Cited by 67 publications

(25 citation statements)

References 24 publications

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“…Ephrin-B3 levels were reported to be increased in ovarian carcinoma, neuroblastoma and glioblastoma compared to corresponding normal tissue [22]. Studies of sarcoma specimens are to date limited to a small series of osteosarcomas, in which EFNB3 mRNA was not found [23]. …”

Section: Discussionmentioning

confidence: 99%

Gene expression signatures differentiate uterine endometrial stromal sarcoma from leiomyosarcoma

Davidson

Abeler

Hellesylt

et al. 2013

Gynecologic Oncology

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Objective Endometrial stromal sarcoma (ESS) and leiomyosarcoma (LMS) are the two most common uterine sarcomas, but both are rare tumors. The aim of the present study was to compare the global gene expression patterns of ESS and LMS. Methods Gene expression profiles of 7 ESS and 13 LMS were analyzed using the HumanRef-8 BeadChip from Illumina. Differentially expressed candidate genes were validated using quantitative real-time PCR and immunohistochemistry. Results Unsupervised hierarchical clustering using all 54,675 genes in the array separated ESS from LMS samples. We identified 549 unique probes that were significantly differentially expressed in the two malignancies by greater than 2-fold with 1% FDR cutoff using one-way ANOVA with Benjamini–Hochberg correction, of which 336 and 213 were overexpressed in ESS and LMS, respectively. Genes overexpressed in ESS included SLC7A10, EFNB3, CCND2, ECEL1, ITM2A, NPW, PLAG1 and GCGR. Genes overexpressed in LMS included CDKN2A, FABP3, TAGLN, JPH2, GEM, NAV2 and RAB23. The top 100 genes overexpressed in LMS included those coding for myosin light chain and caldesmon, but not the genes coding for desmin or actin. CD10 was not overexpressed in ESS. Results for selected genes were validated by quantitative real-time PCR and immunohistochemistry. Conclusions We present the first study in which gene expression profiling was shown to distinguish between ESS and LMS. The molecular signatures unique to each of these malignancies may aid in expanding the diagnostic battery for their differentiation, and may provide a molecular basis for prognostic studies and therapeutic target discovery.

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Section: Discussionmentioning

confidence: 99%

Gene expression signatures differentiate uterine endometrial stromal sarcoma from leiomyosarcoma

Davidson

Abeler

Hellesylt

et al. 2013

Gynecologic Oncology

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“…On the other hand, in fibrosarcomas neither PDGF-R nor b-catenin are dephosphorylated by LMW-PTP which is conversely active on EphA2 receptor. The EphA2 receptor is overexpressed in a large number of cancers, including breast, prostate, and lung carcinomas together with melanomas and sarcomas (Easty et al, 1995;Zelinski et al, 2001;Varelias et al, 2002). In addition to its overexpression, EphA2 is functionally altered in transformed cells by regulating its tyrosine phosphorylation level.…”

Section: Discussionmentioning

confidence: 99%

LMW-PTP is a positive regulator of tumor onset and growth

et al. 2004

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Low molecular weight protein tyrosine phosphatases (LMW-PTPs) are an enzyme family that plays a key role in cell proliferation control by dephosphorylating/ inactivating both tyrosine kinase receptors (such as PDGF, insulin, and ephrin receptors) and docking proteins (such, as b-catenin) endowed with both adhesion and transcriptional activity. Besides being a frequent event in human tumors, overexpression of LMW-PTP has been recently demonstrated to be sufficient to induce neoplastic transformation. We recently demonstrated that overexpression of LMW-PTP strongly potentiates the stability of cell-cell contacts at the adherens junction level, which powerfully suggests that LMW-PTP may also contribute to cancer invasivity. Focusing on mechanisms by which LMW-PTP is involved in cancer onset and progression, the emerging picture is that LMW-PTP strongly increases fibronectin-mediated cell adhesion and mobility but, paradoxically, decreases cell proliferation. Nevertheless, LMW-PTP-transfected NIH3T3 fibroblasts engrafted in nude mice induce the onset of larger fibrosarcomas, which are endowed with higher proliferation activity as compared to mock-transfected controls. Quite opposite effects have been obtained with engrafted fibroblasts transfected with a dominant-negative form of LMW-PTP. Notably, in sarcoma extracts, LMW-PTP overexpression greatly influences the ephrin A2 (EphA2) but not PDGF receptor or b-catenin tyrosine phosphorylation. The high association of dephosphorylated EphA2 overexpression with most human cancers and our observation that cell growth stimulation by LMW-PTP overexpression is restricted to the in vivo model, strongly suggest that LMW-PTP oncogenic potential is mediated by its EphA2 tyrosine dephosphorylating activity.

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“…Members have been most strongly been implicated in mediating developmental events, particularly in the central nervous system (Takasu et al 2002) and in erythropoiesis (Suenobu et al 2002). EFNB2 expression has also been associated with cellular proliferation (Batlle et al 2002; Steinle et al 2003), cell migration (Steinle et al 2003), angiogenesis (Noren et al 2004) and the progression of a wide range of human cancers, including malignant melanoma (Vogt et al 1998), small cell lung carcinoma (Tang et al 1999), osteosarcoma (Varelias et al 2002), endometrial cancer (Takai et al 2001), colon/colorectal carcinoma (Liu et al 2004) and breast cancer (Noren et al 2004). In fact, the capacity of the EFNB2 ligand to increase the potential for growth, tumourigenicity and metastasis in many of these tumour cells is becoming increasingly apparent (Noren et al 2004; Takai et al 2001; Vogt et al 1998).…”

Section: Discussionmentioning

confidence: 99%

The Anti-tumour Agent, Cisplatin, and its Clinically Ineffective Isomer, Transplatin, Produce Unique Gene Expression Profiles in Human Cells

Galea

Murray

2008

Cancer Inform

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Cisplatin is a DNA-damaging anti-cancer agent that is widely used to treat a range of tumour types. Despite its clinical success, cisplatin treatment is still associated with a number of dose-limiting toxic side effects. The purpose of this study was to clarify the molecular events that are important in the anti-tumour activity of cisplatin, using gene expression profiling techniques. Currently, our incomplete understanding of this drug’s mechanism of action hinders the development of more efficient and less harmful cisplatin-based chemotherapeutics. In this study the effect of cisplatin on gene expression in human foreskin fibroblasts has been investigated using human 19K oligonucleotide microarrays. In addition its clinically inactive isomer, transplatin, was also tested. Dualfluor microarray experiments comparing treated and untreated cells were performed in quadruplicate. Cisplatin treatment was shown to significantly up- or down-regulate a consistent subset of genes. Many of these genes responded similarly to treatment with transplatin, the therapeutically inactive isomer of cisplatin. However, a smaller proportion of these transcripts underwent differential expression changes in response to the two isomers. Some of these genes may constitute part of the DNA damage response induced by cisplatin that is critical for its anti-tumour activity. Ultimately, the identification of gene expression responses unique to clinically active compounds, like cisplatin, could thus greatly benefit the design and development of improved chemotherapeutics.

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Human osteosarcoma expresses specific ephrin profiles

Cited by 67 publications

References 24 publications

Gene expression signatures differentiate uterine endometrial stromal sarcoma from leiomyosarcoma

Gene expression signatures differentiate uterine endometrial stromal sarcoma from leiomyosarcoma

LMW-PTP is a positive regulator of tumor onset and growth

The Anti-tumour Agent, Cisplatin, and its Clinically Ineffective Isomer, Transplatin, Produce Unique Gene Expression Profiles in Human Cells

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