Identification of specific reachable molecular targets in human breast cancer using a versatile <b><i>ex vivo</i></b> proteomic method

Castronovo, Vincenzo; Kischel, Philippe; Guilhot, François; Leval, Laurence de; Deféchereux, Thierry; Pauw, Edwin De; Neri, Dario; Waltregny, David

doi:10.1002/pmic.200600888

Cited by 29 publications

(40 citation statements)

References 41 publications

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“…Versican is a highly conserved structural component of the ECM that is involved in neuronal development (4)(5)(6)(7)(8), the inflammatory phase of pulmonary-vascular diseases, atherosclerosis (9)(10)(11)(12), and the invasive and metastatic signatures of many cancers (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Four isoforms or spliced variants have been reported for versican, and the roles of V0, V1, and V3 and to a lesser extent V2 isoforms are recognized in cancer, vascular disease, and neuronal development (detailed in refs.…”

Section: Introductionmentioning

confidence: 99%

RhoGDI2 suppresses lung metastasis in mice by reducing tumor versican expression and macrophage infiltration

Said¹,

Sänchez‐Carbayo²,

Smith³

et al. 2012

J. Clin. Invest.

131

110

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Half of patients with muscle-invasive bladder cancer develop metastatic disease, and this is responsible for most of the deaths from this cancer. Low expression of RhoGTP dissociation inhibitor 2 (RhoGDI2; also known as ARHGDIB and Ly-GDI) is associated with metastatic disease in patients with muscle-invasive bladder cancer. Moreover, a reduction in metastasis is observed upon reexpression of RhoGDI2 in xenograft models of metastatic cancer. Here, we show that RhoGDI2 suppresses lung metastasis in mouse models by reducing the expression of isoforms V1 and V3 of the proteoglycan versican (VCAN; also known as chondroitin sulfate proteoglycan 2 [CSPG2]). In addition, we found that high versican levels portended poor prognosis in patients with bladder cancer. The functional importance of tumor expression of versican in promoting metastasis was established in in vitro and in vivo studies in mice that implicated a role for the chemokine CCL2 (also known as MCP1) and macrophages. Further analysis indicated that RhoGDI2 suppressed metastasis by altering inflammation in the tumor microenvironment. In summary, we demonstrate what we believe to be a new mechanism of metastasis suppression that works by reducing host responses that promote metastatic colonization of the lung. Therapeutic targeting of these interactions may provide a novel adjuvant strategy for delaying the appearance of clinical metastasis in patients. IntroductionOne-half of patients with muscle-invasive (MI) urothelial cancer (UC) of the bladder develop distant metastases, even after radical surgery of the primary tumors. We identified RhoGTP dissociation inhibitor 2 (RhoGDI2; also known as ARHGDIB and Ly-GDI, and abbreviated herein as GDI2) as an invasion and metastasis suppressor in human bladder cancer cell lines (1) and have shown that its expression is inversely associated with clinical outcome after treatment of MI tumors (2). Independently, in comparative gene expression profiling of invasive bladder cancer cell lines and human MI UC samples, we identified versican (VCAN; also known as chondroitin sulfate proteoglycan 2, [CSPG2]) as highly expressed in invasive and metastatic cancers (3).Versican is a highly conserved structural component of the ECM that is involved in neuronal development (4-8), the inflammatory phase of pulmonary-vascular diseases, atherosclerosis (9-12), and the invasive and metastatic signatures of many cancers (13-25). Four isoforms or spliced variants have been reported for versican, and the roles of V0, V1, and V3 and to a lesser extent V2 isoforms are recognized in cancer, vascular disease, and neuronal development (detailed in refs. 8, 26, 27, and the references cited therein). These isoforms contribute to proliferative, adhesive, and migratory states of tumor cells and modulate their interactions with stroma in the tumor microenvironment (26,28,29).Versican expression is regulated by cytokines, chemokines, and hypoxia (6, 7, 9-12, 21, 26, 29-36) via transcription factors such as TCF-4, SP-1, AP-1, and p53, which have bin...

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Section: Introductionmentioning

confidence: 99%

RhoGDI2 suppresses lung metastasis in mice by reducing tumor versican expression and macrophage infiltration

Said¹,

Sänchez‐Carbayo²,

Smith³

et al. 2012

J. Clin. Invest.

131

110

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“…This also applies to samples from cerebrospinal, synovial, and body cavity fluids. The poor accessibility of tissue is reflected by the fact that to date proteomic studies using tissue samples are rare (5,6). However, as outlined recently by Lescuyer et al (7), such approaches may be more successful than serum (or plasma)-based approaches, which, as the authors point out, have not resulted in measurable diagnostic success to date.…”

Section: Source Of Specimenmentioning

confidence: 76%

Urinary Proteome Analysis using Capillary Electrophoresis Coupled to Mass Spectrometry: A Powerful Tool in Clinical Diagnosis, Prognosis and Therapy Evaluation

Mischak¹,

Schiffer²,

Zürbig³

et al. 2009

Journal of Medical Biochemistry

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Kratak sadr`aj: Analiza proteoma je postala je mo}no sredstvo za de{ifrovanje (pato)fiziolo{kih procesa, {to je za rezultat imalo uspostavljanje oblasti klini~ke proteomike. Jedan od glavnih ciljeva je otkrivanje biomarkera oboljenja iz tkiva i telesnih te~nosti. Zbog ogromne slo`enosti pro teoma, pri proteomskoj analizi zasnovanoj na masenoj spektrometriji potrebno je izvr{iti separaciju. U radu su opisane prednosti i ograni~enja proteomske analize pri separaciji proteina putem dvodimenzionalne gel elektroforeze, te~ne hromatografije, SELDI i kapilarne elektroforeze (KE), sa fokusom na KE-MS. KE-MS omogu}ava separaciju i detekciju proteoma male molekularne te`ine u biolo{kim te~nostima uz visoku reproducibilnost i preciznost u samo jednom koraku radnog postupka i za kratko vreme. Po{to pojedina~ni senzitivni i specifi~ni biomarkeri mo`da i ne postoje, strategija za premo{}ivanje te dijagnosti~ke praznine pomera se sa detekcije pojedina~nog analita na simultanu analizu vi{e analita koji zajedno ~ine obrazac specifi~an za dato oboljenje. Takvi pristupi, me|utim, nose sa sobom dodatne izazove, koje }emo predstaviti u ovom radu. Pored izbora odgovaraju}ih tehnolo{kih platformi, neophodan je visok nivo standar dizacije proteomskih merenja i obrade podataka kako bi se vr{ilo profilisanje proteoma. U tom pogledu, zahtevi koji se ti~u nacrta studija, izbora primeraka uzoraka, analize proteomskih podataka i klini~ke evaluacije trebalo bi da budu razmotreni pre izvo|enja proteomske studije.Klju~ne re~i: klini~ka proteomika, kapilarna elektro foreza, masena spektrometrija, biomarker, urin Summary: Proteome analysis has emerged as a powerful tool to decipher (patho)physiological processes, resulting in the establishment of the field of clinical proteomics. One of the main goals is to discover biomarkers for diseases from tissues and body fluids. Due to the enormous complexity of the proteome, a separation step is required for mass spectrometry (MS)-based proteome analysis. In this review, the advantages and limitations of protein separation by two-dimensional gel electrophoresis, liquid chromatography, surface-enhanced laser desorption/ionization and capillary electrophoresis (CE) for proteomic analysis are described, focusing on CE-MS. CE-MS enables separation and detection of the small molecular weight proteome in biological fluids with high reproducibility and accuracy in one single processing step and in a short time. As sensitive and specific single biomarkers generally may not exist, a strategy to overcome this diagnostic void is shifting from single analyte detection to simultaneous analysis of multiple analytes that together form a disease-specific pattern. Such approaches, however, are accompanied with additional challenges, which we will outline in this review. Besides the choice of adequate technological platforms, a high level of standardization of proteomic measurements and data processing is also necessary to establish proteomic profiling. In this regard, demands concerning study design, choice of specimens, ...

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“…One widely used reagent in proteomic research is (Jacquemier et al, 2005;Castronovo et al, 2007;Gonçalves et al, 2008;Montazery-Kordy et al, 2008;Fan et al, 2010;Hooshmand et al, 2013) Fibrinogen A Fragment; S100A9; 21-protein signature; GCDFP-15 AAG; PARK7; S10A7; GDIR; DDAH1; DDAH2; Versican core protein precursor; AGR2; Ubiquitin; Ferritin light chain; CD13, OSF-2; RS/DJ-1 autoantibody Esophageal cancer (Fujita et al, 2006;Hatakeyama et al, 2006;Jazii, Najafi et al, 2006;Uemura et al, 2009;Moghanibashi, Jazii et al 2012;Moghanibashi et al, 2013) Peroxiredoxin VI autoantibody; Alpha -actinin 4; 67 ku laminin receptor; Rho GDP dissociation inhibitor 2; alpha-enolase ; Lamin A/C; nucleodisediphosphate kinase A Gastric cancer (Bai et al, 2011;Kočevar et al, 2012;Sousa et al, 2012;Karimi et al, 2014) α1-antitrypsin precursor; Pepsinogen C; Cathepsin B; MAWBP; Vimentin; galectin 1; DEAD-box protein 48 autoantibody; hnRNP A2/B1…”

Section: Necessary Equipment and Technologies For Cancer Proteomics Amentioning

confidence: 99%

Implementation of Proteomics for Cancer Research: Past, Present, and Future

Karimi

Shahrokni²,

Ranjbar³

2014

Asian Pacific Journal of Cancer Prevention

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Cancer is the leading cause of the death, accounts for about 13% of all annual deaths worldwide. Many different fields of science are collaborating together studying cancer to improve our knowledge of this lethal disease, and find better solutions for diagnosis and treatment. Proteomics is one of the most recent and rapidly growing areas in molecular biology that helps understanding cancer from an omics data analysis point of view. The human proteome project was officially initiated in 2008. Proteomics enables the scientists to interrogate a variety of biospecimens for their protein contents and measure the concentrations of these proteins. Current necessary equipment and technologies for cancer proteomics are mass spectrometry, protein microarrays, nanotechnology and bioinformatics. In this paper, we provide a brief review on proteomics and its application in cancer research. After a brief introduction including its definition, we summarize the history of major previous work conducted by researchers, followed by an overview on the role of proteomics in cancer studies. We also provide a list of different utilities in cancer proteomics and investigate their advantages and shortcomings from theoretical and practical angles. Finally, we explore some of the main challenges and conclude the paper with future directions in this field.

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Identification of specific reachable molecular targets in human breast cancer using a versatile ex vivo proteomic method

Cited by 29 publications

References 41 publications

RhoGDI2 suppresses lung metastasis in mice by reducing tumor versican expression and macrophage infiltration

RhoGDI2 suppresses lung metastasis in mice by reducing tumor versican expression and macrophage infiltration

Urinary Proteome Analysis using Capillary Electrophoresis Coupled to Mass Spectrometry: A Powerful Tool in Clinical Diagnosis, Prognosis and Therapy Evaluation

Implementation of Proteomics for Cancer Research: Past, Present, and Future

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