Detection of Amplifiable mRNA Extracellular to Insulin-Producing Cells: Potential for Predicting Beta Cell Mass and Function

Rani, Sweta; Clynes, Martin; O’Driscoll, Lorraine

doi:10.1373/clinchem.2007.087973

Cited by 13 publications

(14 citation statements)

References 21 publications

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“…This observation reflected that of the cells themselves. This is in keeping with our previous observations from a range of cell lines (16,17,19) and pilot study analysis of serum and corresponding tumor tissue from patients with breast cancer (18). These findings indicate that full-length mRNAs can be selectively expelled from cells.…”

Section: Discussionsupporting

confidence: 91%

“…Predictive biomarkers for HER-targeting drugs (ideally extracellular, minimally invasive) are needed for improved patient selection and thus enhanced patient outcome, as are novel therapeutic strategies to circumvent resistance. Our previous studies indicate that analyzing extracellular RNAs in medium conditioned by cells can be a useful starting point to identifying potential biomarkers, some proving to have functional relevance within the cell (16)(17)(18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

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Neuromedin U: A Candidate Biomarker and Therapeutic Target to Predict and Overcome Resistance to HER-Tyrosine Kinase Inhibitors

et al. 2014

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Intrinsic and acquired resistance to HER-targeting drugs occurs in a significant proportion of HER2-overexpressing breast cancers. Thus, there remains a need to identify predictive biomarkers that could improve patient selection and circumvent these types of drug resistance. Here, we report the identification of neuromedin U (NmU) as an extracellular biomarker in cells resistant to HER-targeted drugs. NmU overexpression occurred in cells with acquired or innate resistance to lapatinib, trastuzumab, neratinib, and afatinib, all of which displayed a similar trend upon short-term exposure, suggesting NmU induction may be an early response. An analysis of 3,489 cases of breast cancer showed NmU to be associated with poor patient outcome, particularly those with HER2-overexpressing tumors independent of established prognostic indicators. Ectopic overexpression of NmU in drug-sensitive cells conferred resistance to all HER-targeting drugs, whereas RNAi-mediated attenuation sensitized cells exhibiting acquired or innate drug resistance. Mechanistic investigations suggested that NmU acted through HSP27 as partner protein to stabilize HER2 protein levels. We also obtained evidence of functional NmU receptors on HER2-overexpressing cells, with the addition of exogenous NmU eliciting an elevation in HER2 and EGFR expression along with drug resistance. Finally, we found that NmU seemed to function in cell motility, invasion, and anoikis resistance. In vivo studies revealed that NmU attenuation impaired tumor growth and metastasis. Taken together, our results defined NmU as a candidate drug response biomarker for HER2-overexpressing cancers and as a candidate therapeutic target to limit metastatic progression and improve the efficacy of HER-targeted drugs. Cancer Res; 74(14); 3821-33. Ó2014 AACR.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Neuromedin U: A Candidate Biomarker and Therapeutic Target to Predict and Overcome Resistance to HER-Tyrosine Kinase Inhibitors

et al. 2014

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“…Following RNA isolation, 32 reverse transcription (RT) was performed using the TaqMan microRNA reverse transcription kit (Applied Biosystems). Briefly, the RT reaction consisted of 1.5 µL 10 × RT Buffer, 0.15 µL dNTPs 100 mM, 0.19 µL RNase Inhibitor 20 U/µL, 1.0 MultiScribe reverse transcriptase, 3 µL of RT primer and total RNA (10 ng from cells or 5 µl of RNA from conditioned media), in a final volume of 15 µL.…”

Section: Methodsmentioning

confidence: 99%

Comparative antiproliferative effects of iniparib and olaparib on a panel of triple-negative and non-triple-negative breast cancer cell lines

Pierce

McGowan

Cotter

et al. 2013

Cancer Biology & Therapy

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“…It has been reported that bone marrow desmohaemoblasts can differentiate into endodermal IPCs. 9 Considering the similarity between PMSCs and bone marrow mesenchymal stem cells, it would seem to be feasible for PMSCs to have the ability to differentiate into IPCs. Indeed, flow cytometry analysis of PMSCs has revealed that these cells express CD29, CD44 and CD105, but not CD34, CD45 or CD19, indicating that they are not fibroblast epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Differentiation of Human Placenta-derived Adherent Cells into Insulin-producing Cells

Sun

2009

J Int Med Res

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This study investigated the differentiation of placenta-derived adherent cells (PDACs) into insulin-producing cells (IPCs). PDACswere cultured and the cells characterized by analysis of cell surface markers using flow cytometry. The PDACs were then treated with induction media containing basic fibroblast growth factor (bFGF) and bmercaptoethanol (b-ME). After induction, the presence of IPCs was demonstrated using dithizone staining, and the production of functional insulin was confirmed using immunocytochemistry and an enzyme-linked immunosorbent assay. Expression of the islet-associated genes PDX-1, Insulin 1, Insulin 2 and Glut 2 in the induced cells was measured using a reverse transcription-polymerase chain reaction; PDX-1 was expressed after 7 days of induction and PDX-1, Insulin 1 and Insulin 2 were all detected after 14 days. These results suggest that the placenta could be a new source of stem cells that can be induced to differentiate into IPCs following treatment with media containing bFGF and b-ME.

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Detection of Amplifiable mRNA Extracellular to Insulin-Producing Cells: Potential for Predicting Beta Cell Mass and Function

Cited by 13 publications

References 21 publications

Neuromedin U: A Candidate Biomarker and Therapeutic Target to Predict and Overcome Resistance to HER-Tyrosine Kinase Inhibitors

Neuromedin U: A Candidate Biomarker and Therapeutic Target to Predict and Overcome Resistance to HER-Tyrosine Kinase Inhibitors

Comparative antiproliferative effects of iniparib and olaparib on a panel of triple-negative and non-triple-negative breast cancer cell lines

In Vitro Differentiation of Human Placenta-derived Adherent Cells into Insulin-producing Cells

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