Quantitative Proteomic Analysis in Metastatic Renal Cell Carcinoma Reveals a Unique Set of Proteins with Potential Prognostic Significance

Masui, Olena; White, Nicole M.; DeSouza, Leroi V.; Krakovska, Olga; Matta, Ajay; Metias, Shereen; Khalil, Bishoy; Romaschin, Alexander D.; Honey, R. John D'a.; Stewart, Robert; Pace, Kenneth T.; Bjarnason, Georg A.; Siu, Kin Wai Michael; Yousef, George M.

doi:10.1074/mcp.m112.020701

Cited by 67 publications

(83 citation statements)

References 97 publications

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“…28 These observations imply that endogenous Gal-1 may play an important role in RCC progression. Although it has been reported that metastatic RCC tissues with poor prognosis show higher Gal-1 expression, 18 the molecular mechanisms of Gal-1 in progression of RCC still remain unclear.…”

Section: Discussionmentioning

confidence: 99%

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Galectin-1 Upregulates CXCR4 to Promote Tumor Progression and Poor Outcome in Kidney Cancer

Huang

Tang

Chung

et al. 2014

Journal of the American Society of Nephrology

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Galectin-1, a b-galactoside-binding lectin, is involved in many physiologic and pathologic processes, including cell adhesion, differentiation, angiogenesis, and tumor progression. However, the role of galectin-1 in kidney cancer remains elusive. This study evaluated the role of galectin-1 in the progression and clinical prognosis of renal cell carcinoma. We found significant overexpression of galectin-1 in both kidney cancer cell lines and metastatic tissue specimens from patients with renal cell carcinoma. Knockdown of galectin-1 gene expression in renal cancer cell lines reduced cell invasion, clonogenic ability, and epithelial-mesenchymal transition in vitro; reduced tumor outgrowth in vivo; and inhibited the angiogenesis-inducing activity of these cells in vitro and in vivo. Galectin-1 knockdown decreased CXCR4 expression levels in kidney cancer cells, and restoration of CXCR4 expression in galectin-1-silenced cells rescued cell motility and clonogenic ability. Additional studies suggested that galectin-1 induced CXCR4 expression through activation of nuclear factor-kB (NF-kB). Analysis of patient specimens confirmed the clinical significance and positive correlation between galectin-1 and CXCR4 expression levels and revealed concomitant overexpression of galectin-1 and CXCR4 associated adversely with overall and disease-free survival. Our findings suggest that galectin-1 promotes tumor progression through upregulation of CXCR4 via NF-kB. The coordinated upregulation of galectin-1 and CXCR4 may be a novel prognostic factor for survival in patients with renal cell carcinoma and the galectin-1-CXCR4 axis may serve as a therapeutic target in this disease. 25: 148625: -149525: , 201425: . doi: 10.1681 Renal cell carcinoma (RCC) accounts for approximately 4% of all adult malignancies. 1 More than one third of patients will present with locally advanced or metastatic disease at the time of diagnosis. 2 The 5-year survival rate of metastatic RCC is only 10% because of resistance to chemotherapy and radiation therapy. 3 Although cytokine therapy with IFN-a and IL-2 is the gold standard treatment, its overall efficacy rate is limited by its significant toxicity. 4 Recently, several molecular targeting drugs, including sunitinib and temsirolimus, have been approved for advanced RCC. 4 However, treatment response is not long-standing and overall survival remains poor. Thus, the identification of novel molecular targets in RCC is urgently needed for the development of effective therapies. J Am Soc Nephrol

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Section: Discussionmentioning

confidence: 99%

“…15,16 Previous studies have suggested that Gal-1 may serve as a potential marker for RCC. 17,18 However, the detailed molecular mechanisms connecting Gal-1 to RCC remain largely unknown. The present study examined whether Gal-1 contributed to functional implications and clinical relevance in kidney cancer pathogenesis.…”

mentioning

confidence: 99%

Galectin-1 Upregulates CXCR4 to Promote Tumor Progression and Poor Outcome in Kidney Cancer

Huang

Tang

Chung

et al. 2014

Journal of the American Society of Nephrology

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“…Dysregulated protein expression in Cyld knockout kidney samples was verified by Western blot analysis as described before (Masui et al, 2013). The proteins used (and their antibodies) were: Hsd17b4 (Abcam ab170910) and AKR1B3 (ABcam ab175394).…”

Section: Western Blot Analysismentioning

confidence: 99%

Proteomic analysis revealed the altered kidney protein profile of a Cyld knockout mouse model

et al. 2015

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ABSTRACT. The aim of this study was to compare the proteomics pattern of the kidneys from Cyld knockout mice with that from normal mouse kidneys and establish a preliminary understanding of the role of Cyld in the kidney. Proteins from the kidneys of knockout Cyld mice and wild-type mice were extracted, isobaric tags for relative and absolute quantitation (iTRAQ) was performed, and the proteomics patterns of the two groups were compared. The genotypes of the mice were verified by polymerase chain reaction. A total of 1748 proteins with a local false discovery rate of ≤5% were identified, among which 1437 proteins were reliably recognized and quantified. The expression of two dysregulated proteins was confirmed by Western blotting. Gene ontology and pathway analyses indicated that the proteins identified were involved in biological processes, cell components, and molecular functions, and participated in different pathways. Some of the proteins identified were relevant to renal function or kidney diseases. The difference between the proteomics profiles of kidneys from Cyld knockout mice and wild-type mice was prominent, which correlates to kidney dysfunction and the development of renal diseases.

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“…ITRAQ label technology together with nano liquid chromatography-mass spectrometry (NanoLC-MS/MS) has proven to be efficient in protein analysis (13)(14)(15). Hence, the clinic-combined metastatic model and this technological means will increase the likeliness of discovering new metastasis-associated genes (16) and proteins (17) for identifying new antitumor targets.…”

Section: Introductionmentioning

confidence: 99%

Establishment of a highly metastatic model with a newly isolated lung adenocarcinoma cell line

Cui

Geng

et al. 2015

International Journal of Oncology

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Abstract. Lung cancer is the leading cause of malignancyrelated death worldwide, and metastasis always results in a poor prognosis. However, therapeutic progress is hampered by a deficiency of appropriate pre-clinical metastatic models. To bridge this experimental gap, we developed an in vivo metastatic model via subcutaneous (s.c.) injection. The original cell line (XL-2) adopted in this model was newly isolated from the ascites of a patient with extensive metastases of lung adenocarcinoma, thereby avoiding any alteration of its initial molecular biology features from artificial serial cultivation. After comprehensive phenotypical and histological analysis, it was identified as a lung adenocarcinoma cell line. Additionally, the drug test showed that XL-2 cell line was sensitive to docetaxel, and resistant to doxorubicin, indicating it might serve as a cell line model of drug resistance for identifying mechanisms of tumors resistant to doxorubicin. Through this s.c. model, we further obtained a highly metastatic cell line (designated XL-2sci). The metastatic rate of mice in XL-2 group was 3/10, in contrast to the rate of 9/10 in XL-2sci group. Optical imaging, micro-computed tomography (micro-CT) scanning and Transwell assays were further applied to identify the enhanced metastatic capacity of Xl-2sci cells both in vivo and in vitro. Compared with XL-2 cells, ITRAQ labeled proteomics profiling study showed that some tumor metastasisassociated proteins were upregulated in XL-2sci cells, which also indicated the reliability of our model. Proliferation ability of XL-2 and XL-2sci were also evaluated. Results showed that highly metastatic XL-2sci possessed a decreased proliferation capacity versus XL-2, which demonstrated that its increased metastatic activity was not facilitated by a faster growth rate.In conclusion, we successfully developed an in vivo metastatic model using a newly established lung adenocarcinoma cell line, which will be beneficial to further investigations of lung cancer metastasis and to the development of anti-metastasis drugs.

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Quantitative Proteomic Analysis in Metastatic Renal Cell Carcinoma Reveals a Unique Set of Proteins with Potential Prognostic Significance

Cited by 67 publications

References 97 publications

Galectin-1 Upregulates CXCR4 to Promote Tumor Progression and Poor Outcome in Kidney Cancer

Galectin-1 Upregulates CXCR4 to Promote Tumor Progression and Poor Outcome in Kidney Cancer

Proteomic analysis revealed the altered kidney protein profile of a Cyld knockout mouse model

Establishment of a highly metastatic model with a newly isolated lung adenocarcinoma cell line

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