Tumorigenic properties of alternative osteopontin isoforms in mesothelioma

Ivanov, Sergey V.; Ivanova, Alla V.; Goparaju, Chandra; Chen, Yuanbin; Beck, Amanda K.; Pass, Harvey I.

doi:10.1016/j.bbrc.2009.03.042

Cited by 39 publications

(38 citation statements)

References 10 publications

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“…Therefore, our data indicate that OPNc isoform is specifically expressed in ovarian tumor samples, as previously described for breast cancer cells (16,17). In contrast, OPNc is barely detected in mesothelioma tumors and in lung cancer samples, whereas OPNa and OPNb showed upregulation in these samples (18,19). Our data further support previous findings showing that OPN isoforms present tumor-specific expression patterns.…”

Section: Discussionsupporting

confidence: 92%

“…These findings suggest that OPN isoforms present differential expression patterns in tumor and nontumor ovarian samples, with OPNc only expressed in tumor samples. These data, together with previous reports showing that OPN isoforms have tumor-specific expression and functional properties (16)(17)(18)(19), prompted us to investigate their functional roles in ovarian cancer biology.…”

Section: Resultsmentioning

confidence: 90%

“…Ovarian malignant transformation is caused by genetic modifications that disrupt the regulation of proliferation, programmed cell death and senescence, but the specific genetic pathways involved in these processes are poorly understood (34,35). Alternative pre-mRNA splicing is an important molecular mechanism associated with tumorigenesis and cancer progression (36) and has been shown to be one of the mechanisms by which cancer cells alter the structure and function of OPN (16)(17)(18)(19)37). Based on these assumptions, we believe that describing the functional significance of OPN splicing isoforms in ovarian cancer would improve the understanding of signaling pathways involved in the progression of this complex neoplasic disease.…”

Section: Discussionmentioning

confidence: 99%

“…Based on these assumptions, we believe that describing the functional significance of OPN splicing isoforms in ovarian cancer would improve the understanding of signaling pathways involved in the progression of this complex neoplasic disease. Alternative splicing of OPN has been described in mesothelioma, breast cancer, hepatocellular carcinoma, glioma, lung cancer and head and neck squamous cell carcinoma (HNSCC) and the roles of different splicing isoforms on cancer growth and progression has been reported (16)(17)(18)(19)37). However, OPN splicing and its resulting products has not been examined previously in ovarian cancer.…”

Section: Discussionmentioning

confidence: 99%

“…OPNa is the full-length isoform, whereas OPNb lacks exon 5 and OPNc lacks exon 4 (15). OPN splicing isoforms present tissue and tumor-specific roles (16)(17)(18)(19). All current available data about OPN in ovarian cancer relates to OPN in general, without distinguishing among the various isoforms, and OPN splicing in this tumor has not been characterized previously.…”

Section: Introductionmentioning

confidence: 94%

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Osteopontin-c Splicing Isoform Contributes to Ovarian Cancer Progression

Tilli

Franco²,

Robbs³

et al. 2011

Molecular Cancer Research

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Ovarian carcinoma is one of the most aggressive gynecological diseases and generally diagnosed at advanced stages. Osteopontin (OPN) is one of the proteins overexpressed in ovarian cancer and is involved in tumorigenesis and metastasis. Alternative splicing of OPN leads to 3 isoforms, OPNa, OPNb, and OPNc. However, the expression pattern and the roles of each of these isoforms have not been previously characterized in ovarian cancer. Herein, we have evaluated the expression profiling of OPN isoforms in ovarian tumor and nontumor samples and their putative roles in ovarian cancer biology using in vitro and in vivo functional assays. OPNa and OPNb were expressed both in tumor and nontumor ovarian samples, whereas OPNc was specifically expressed in ovarian tumor samples. The isoform OPNc significantly activated OvCar-3 cell proliferation, migration, invasion, anchorage-independent growth and tumor formation in vivo. Additionally, we have also shown that some of the OPNc-dependent protumorigenic roles are mediated by PI3K/Akt signaling pathway. OPNc stimulated immortalized ovarian epithelial IOSE cell proliferation, indicating a role for this isoform in ovarian cancer tumorigenesis. Functional assays using OPNc conditioned medium and an anti-OPNc antibody have shown that most cellular effects observed herein were promoted by the secreted OPNc. According to our data, OPNc-specific expression in ovarian tumor samples and its role on favoring different aspects of ovarian cancer progression suggest that secreted OPNc contributes to the physiopathology of ovarian cancer progression and tumorigenesis. Altogether, the data open possibilities of new therapeutic approaches for ovarian cancer that selectively down regulate OPNc, altering its properties favoring ovarian tumor progression. Mol Cancer Res; 9(3); 280-93. Ó2011 AACR.

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Section: Discussionsupporting

confidence: 92%

Section: Resultsmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

See 3 more Smart Citations

Osteopontin-c Splicing Isoform Contributes to Ovarian Cancer Progression

Tilli

Franco²,

Robbs³

et al. 2011

Molecular Cancer Research

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Prognostic risk assessment model for alternative splicing events and splicing factors in malignant pleural mesothelioma

et al. 2022

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Background Malignant pleural mesothelioma (MPM) is a rare and highly malignant thoracic tumor. Although alternative splicing (AS) is associated with tumor prognosis, the prognostic significance of AS in MPM is unknown. Methods Transcriptomic data, clinical information, and splicing percentage values for MPM were obtained from The Cancer Genome Atlas (TCGA) and TCGA SpliceSeq databases. Least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox analyses were performed to establish a model affecting the prognosis of MPM. Survival and ROC analyses were used to test the effects of the prognostic model. LASSO/multivariate Cox analysis was used to construct the MPM prognostic splicing factor (SF) model. The SF–AS interaction network was analyzed using Spearman correlation and visualized using Cytoscape. The association between the MPM prognostic SF model and drug sensitivity to chemotherapeutic agents such as cisplatin was analyzed using pRRophetic.R. Results The LASSO/multivariate Cox analysis identified 41 AS events and 2 SFs that were mostly associated with survival. Nine prognostic prediction models (i.e., seven types of AS model, total AS model, and SF model) were developed. An MPM prognostic SF–AS regulatory network was subsequently constructed with decreased drug sensitivity in the SF model high‐risk group (p = 0.025). Conclusion This study provides the first comprehensive analysis of the prognostic value of AS events and SFs in MPM. The SF–AS regulatory network established in this study and our drug sensitivity analysis using the SF model may provide novel targets for pharmacological studies of MPM.

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The Role of Inflammation in Sarcoma

Radons

2014

Advances in Experimental Medicine and Biology

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Sarcomas encompass a heterogenous group of tumors with diverse pathologically and clinically overlapping features. It is a rarely curable disease, and their management requires a multidisciplinary team approach. Chronic inflammation has emerged as one of the hallmarks of tumors including sarcomas. Classical inflammation-associated sarcomas comprise the inflammatory malignant fibrous histiocytoma and Kaposi sarcoma. The identification of specific chromosomal translocations and important intracellular signaling pathways such as Ras/Raf/MAPK, insulin-like growth factor, PI3K/AKT/mTOR, sonic hedgehog and Notch together with the increasing knowledge of angiogenesis has led to development of targeted therapies that aim to interrupt these pathways. Innovative agents like oncolytic viruses opened the way to design new therapeutic options with encouraging findings. Preclinical evidence also highlights the therapeutic potential of anti-inflammatory nutraceuticals as they can inhibit multiple pathways while being less toxic. This chapter gives an overview of actual therapeutic standards, newest evidence-based studies and exciting options for targeted therapies in sarcomas.

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Tumorigenic properties of alternative osteopontin isoforms in mesothelioma

Cited by 39 publications

References 10 publications

Osteopontin-c Splicing Isoform Contributes to Ovarian Cancer Progression

Osteopontin-c Splicing Isoform Contributes to Ovarian Cancer Progression

Prognostic risk assessment model for alternative splicing events and splicing factors in malignant pleural mesothelioma

The Role of Inflammation in Sarcoma

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