β1 integrin and IL-3R coordinately regulate STAT5 activation and anchorage-dependent proliferation

Defilippi, Paola; Rosso, Arturo; Dentelli, Patrizia; Calvi, Cristina; Garbarino, Giovanni; Tarone, Guido; Pegoraro, Luigi; Brizzi, Maria Felice

doi:10.1083/jcb.200405116

Cited by 35 publications

(33 citation statements)

References 60 publications

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“…Flow cytometry To analyse cell-cycle progression, ECs and EPCs treated for 2 days as indicated were processed by FACS analysis, as previously described by Defilippi et al [22]. Briefly, after treatment, the cells were fixed with 70% (vol./vol.)…”

Section: Methodsmentioning

confidence: 99%

RETRACTED ARTICLE: MIR221/MIR222-driven post-transcriptional regulation of P27KIP1 and P57KIP2 is crucial for high-glucose- and AGE-mediated vascular cell damage

et al. 2011

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Aims/hypothesis MicroRNAs (miRNAs) are a novel group of small non-coding RNAs that regulate gene expression at the post-transcriptional level and act on their target mRNAs in a tissue-and cell-type-specific manner. Herein, the relevance of MIR221/MIR222 in high-glucose-and AGEmediated vascular damage was investigated. Methods Functional studies were performed using human mature endothelial cells and endothelial progenitor cells subjected to high glucose or AGE. Quantitative real-time amplification was performed to analyse MIR221/MIR222 expression in these experimental conditions. Luciferase assay was used to identify MIR221/MIR222 targets. Functional studies were performed in vitro and in vivo in mice using gain-and loss-of-function approaches. Results Using an in vivo mouse model we demonstrated that exposure to AGE and high glucose impaired vessel formation. Moreover, in vitro functional studies revealed that both high glucose and AGE inhibit cell-cycle progression by modulating the expression of P27KIP1 (also known as CDKN1B) and P57KIP2 (also known as CDKN1C), which encode cyclindependent kinase inhibitor 1B (p27, Kip1) (P27KIP1) and cyclin-dependent kinase inhibitor 1C (p57, Kip2) (P57KIP2), respectively. Crucial to AGE-and high-glucose-mediated cellcycle arrest was the downregulation of MIR221/MIR222 expression. Luciferase assay showed that MIR221 and MIR222 specifically bind to the P27KIP1 and P57KIP2 mRNA 3′-untranslated regions, implicating P27KIP1 and P57KIP2 as MIR221/MIR222 targets. These results were confirmed by gainof-function experiments in vitro, and by injecting mice with endothelial cells overexpressing MIR221 and MIR222. Conclusions/interpretation We provide evidence that highglucose-and AGE-induced inhibition of vascular cell proliferation is controlled by MIR221/MIR222-driven posttranscriptional regulation of P27KIP1 and P57KIP2. These data add further insight to the possible contribution of miRNAs in vascular damage mediated by a high-glucose environment.

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Section: Methodsmentioning

confidence: 99%

RETRACTED ARTICLE: MIR221/MIR222-driven post-transcriptional regulation of P27KIP1 and P57KIP2 is crucial for high-glucose- and AGE-mediated vascular cell damage

et al. 2011

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“…Integrin b1-mediated cell adhesion regulates a multitude of cellular responses, including proliferation, survival and cross-talk between different cellular signaling pathways. A collagen-binding integrin a1b1 functions as a negative regulator of epidermal growth factor receptor (EGFR) signaling through the activation of a protein tyrosine phosphatase [22,23]. Integrinmediated cell-ECM interactions play a critical role in cell adhesion, migration and morphogenesis during vertebrate retinal development [24].…”

Section: Discussionmentioning

confidence: 99%

Lipoprotein p37 from Mycoplasma hyorhinis inhibiting mammalian cell adhesion

et al. 2005

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Summaryp37 protein is a membrane lipoprotein of Mycoplasma hyorhinis, and our previous work showed that there was high ratio of M. hyorhinis infection in human gastric carcinoma. To investigate the possible functions of p37 in cancer development, the nucleotide sequence of p37 gene was modified and expressed well in transfected cells. We found that p37 localized at the Golgi apparatus and could be secreted out of the cell. Human gastric cancer cells AGS, after being transfected with the p37 gene, were smaller, more spherical and easy to detach from each other. Their adhesion to matrix was also diminished and cytoskeleton in these stable p37 AGS cell was rearranged and transcription co-factor b-actin was transferred to nucleolus with down-regulation of ICAM-1 and integrin b1. These findings will be helpful for us to elucidate the effects of p37 on eukaryotic cells as well as to better understand the potential relationship between cancer and mycoplasma infection.

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“…To analyze cell-cycle progression, fluorescence-activated cell sorting analysis was performed, as previously described (Defilippi et al, 2005), on NECs, rTECs or mTECs, cultured for 24-48-72 h with 2% of fetal bovine serum, in presence or in absence of the anti-IL-3-neutralizing Ab or the Akt inhibitor, Ly294002, or alternatively on IL-3-or Akt-depleted cells (analyzed 48 h later). Briefly, after treatment, cells were fixed with 70% ethanol, DNA was stained with propidium iodide and analyzed with a flow cytometer (FACSCalibur, Becton Dickinson, San Jose, CA, USA).…”

Section: Flow Cytometrymentioning

confidence: 99%

IL-3 is a novel target to interfere with tumor vasculature

et al. 2011

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Angiogenesis inhibiting agents are currently integral component of anticancer therapy. However, tumors, initially responsive to anti-angiogenic drugs or vascular targeting agents, can acquire resistance. The limited clinical efficacy might result from the heterogeneous nature of tumors or alternatively from the unique phenotype of tumor vascular cells, widely diverse from so-called 'normal' endothelium. Hence, defining the molecular mechanisms driving this diversity might provide a rational basis to design combinatory therapies that should be more effective in avoiding resistance. Herein, we demonstrated that tumor-derived endothelial cells (TECs) isolated from breast and kidney carcinomas retained an endothelial phenotype, but outspread independently of growth factors. Applying small interfering RNA approach, we demonstrated that interleukin (IL)-3, but not vascular endothelial growth factor, released by TECs, supports their autocrine growth and promotes in vivo vessel formation and tumor angiogenesis. Meanwhile, we found that the expression of the membrane-bound kit ligand (mbKitL) depends on IL-3, and it is crucial for adhesion of endothelial progenitor cells (EPCs) and inflammatory cells to TECs. These events required Akt activation. Finally, the finding that depletion of the mbKitL prevented EPC and inflammatory cell trafficking into vascular microenvironment, indicates that, as in bone marrow, the mbKitL can act as a membrane/adhesion molecule for c-Kit-expressing cells. These data provide evidences that an IL-3 autocrine loop can drive a tumor endothelial switch and that targeting IL-3 might confer a significant therapeutic advantage to hamper tumor angiogenesis.

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β1 integrin and IL-3R coordinately regulate STAT5 activation and anchorage-dependent proliferation

Cited by 35 publications

References 60 publications

RETRACTED ARTICLE: MIR221/MIR222-driven post-transcriptional regulation of P27KIP1 and P57KIP2 is crucial for high-glucose- and AGE-mediated vascular cell damage

RETRACTED ARTICLE: MIR221/MIR222-driven post-transcriptional regulation of P27KIP1 and P57KIP2 is crucial for high-glucose- and AGE-mediated vascular cell damage

Lipoprotein p37 from Mycoplasma hyorhinis inhibiting mammalian cell adhesion

IL-3 is a novel target to interfere with tumor vasculature

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