JCI early table of contents for Dec. 17, 2012

December 17, 2012

Harnessing the ID in glioma

Gliomas are the most common form of brain tumor. They are highly aggressive and effective treatments are not currently available. The tumors contain glioma initiating cells (GICs), a population that is highly similar to neural stem cells. GICs drive tumor progression and must stay in a particular extracellular niche in order to maintain their cancer-promoting, stem cell-like characteristics. In this issue of the Journal of Clinical Investigation, researchers led by Antonio Iavarone at Columbia University report on the role of ID proteins in glioma. ID proteins allow stem cells to stay anchored in a particular extracellular niche. Using a mouse model of glioma, Iavarone and colleagues found that ID proteins were also responsible for retaining GICs in the extracellular niche that allowed them to maintain their cancer promoting properties. In human glioma patients, the expression of a group of Id-regulated genes was correlated with clinical outcomes. This results suggest that ID proteins are important regulators of glioma and may be suitable therapeutic targets.


Mesenchymal high-grade glioma is maintained by the ID-RAP1 axis

Antonio Iavarone
Columbia University, New York, NY, USA
Phone: 212-851-5245; Fax: 212-851-5267; E-mail: ai2102@columbia.edu

View this article at: http://www.jci.org/articles/view/63811?key=adbf132bafbabee5f39e

An inflammatory protein plays an unexpected role in lung infections

The immune system responds to infections in the lungs by recruiting neutrophils, a group of immune cells that are responsible for recognizing and eliminating pathogens, to the site of infection. In addition to killing infectious pathogens, neutrophils also drive inflammation, which can lead to poor lung function and sometimes fatal complications. In this issue of the Journal of Clinical Investigation, researchers led by Julia Klesney-Tait at the University of Iowa examined how the loss of the inflammatory protein TREM-1 affected the survival of mice infected with pneumonia. Though they had expected loss of TREM-1 to increase survival by reducing inflammation, Klesney-Tait and colleagues found that mice lacking TREM-1 had increased inflammation and were more likely to die from lung infection. Examination of the lungs of the infected mice showed that neutrophils lacking TREM-1 were unable to migrate to the site of infection. This study identified an unexpected role for TREM-1 in neutrophil migration and indicates that therapeutics targeting TREM-1 may have unintended effects.


Transepithelial migration of neutrophils into the lung requires TREM-1

Julia Klesney-Tait
University of Iowa Carver College of Medicine, Iowa City, IA, USA
Phone: 319-356-3576; Fax: 319-353-6406; E-mail: julia-klesney-tait@uiowa.edu

View this article at: http://www.jci.org/articles/view/64181?key=31f9c8fee5fe0c78ceb9

Breast cancer cells interact with non-cancerous tissue to drive metastasis

In addition to mutations, environmental conditions created by the tissues surrounding tumors (stroma) play a major role in cancer progression. In this issue of the Journal of Clinical Investigation, researchers led by Gregg Semenza at Johns Hopkins University examined the interactions between breast cancer cells and the stroma to identify underlying pro-metastatic molecular mechanisms. They found that both breast cancer cells and the stroma secrete proteins that influence the behavior of each cell type. Additionally, Semenza and colleagues found that a group of proteins known as HIFs were required for stroma-driven metastases, suggesting that drugs which inhibit this class of proteins may be useful in preventing breast cancer metastasis.


Hypoxia-inducible factor-dependent breast cancer-mesenchymal stem cell bidirectional signaling promotes metastasis

Gregg L. Semenza
The Johns Hopkins University School of Medicine, Baltimore, MD, USA
Phone: 1-410-955-1619 (direct); Fax: 1-443-287-5618; E-mail: gsemenza@jhmi.edu

View this article at: http://www.jci.org/articles/view/64993?key=383f15d94b2d345ef83d

Intestinal wound repair relies on ANXA1

The cells that line the intestine, known as the intestinal epithelium, can become injured in disease states such as ulcerative colitis. To repair the injury, epithelial cells must migrate to the wound; however, the signals that drive this migration are unknown. In this issue of the Journal of Clinical Investigation, researchers led by Asma Nusrat and Andrew Neish at Emory University identified signaling pathways that mediate the repair of the intestinal epithelium. Using isolated epithelial cells and a mouse model of intestinal injury, Nusrat, Neish, and colleagues found that the protein ANXA1 promoted epithelial cell migration to mediate wound healing in the intestinal epithelium. Additionally, they found greater levels of this protein in patients with ulcerative colitis. These findings suggest that ANXA1 could potentially be used as a therapeutic agent to promote healing of the intestines in patients with ulcerative colitis.


Annexin A1, formyl peptide receptor, and NOX1 orchestrate epithelial repair

Asma Nusrat
Emory University, Atlanta, GA, USA
Phone: 404-727-8543; Fax: 404-727-3321; E-mail: anusrat@emory.edu

View this article at: http://www.jci.org/articles/view/65831?key=87faeb753f67fc8b39a9

Researchers identify a new player in tumor angiogenesis

Angiogenesis, or the formation of new blood vessels, is important for tumor growth; however, while many regulatory growth factors have been identified, little is known about the genetic regulation that promotes tumor angiogenesis. In this issue of the Journal of Clinical Investigation, researchers led by Injune Kim at the Korea Advanced Institute of Science and Technology examined the expression of SOX17, a protein that regulates gene expression in blood vessel-forming endothelial cells during development. Using a mouse model of tumor angiogenesis, Kim and colleagues found that increased levels of SOX17 promoted tumor angiogenesis, while loss of SOX17 reduced angiogenesis and tumor growth. These results suggest that SOX17 is a potential therapeutic target to decrease angiogenesis and tumor growth.


Sox17 promotes tumor angiogenesis and destabilizes tumor vessels in mice

Injune Kim
KAIST, Daejeon, KOR
Phone: 82-42-350-4238; E-mail: injunek@kaist.ac.kr

View this article at: http://www.jci.org/articles/view/64547?key=6456e85ee577f7d05a66

A trio of microRNAs contributes to liver cancer progression

MicroRNAs are small RNA molecules that regulate the expression of various genes. In this issue of the Journal of Clinical Investigation, researchers led by Shelly Lu at the University of Southern California identified a trio of microRNAs that reduce the expression of MAT1A. Reduced MAT1A expression is correlated with a worse prognosis in hepatocellular carcinoma (HCC; liver cancer). The researchers found that expression of the three microRNAs was induced in human HCC samples. Using a mouse model of HCC, Lu and colleagues demonstrated that reducing expression of these microRNAs resulted in smaller tumors, while increased expression promoted tumor growth and metastasis. These findings show that the trio of microRNAs are important regulators of HCC growth and could potentially serve as therapeutic targets in cancers associated with decreased MAT1A expression.


MicroRNAs regulate methionine adenosyltransferase 1A expression in hepatocellular carcinoma

Shelly Lu
Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Phone: 323-442-2441; Fax: 323-442-3234; E-mail: shellylu@usc.edu

View this article at: http://www.jci.org/articles/view/63861?key=7b5165b049a1f1c9e3aa

MicroRNA drives breast cancer metastasis by promoting cancer cell survival

Tumor metastasis, which accounts for the majority of deaths in breast cancer patients, is a process by which cancer cells acquire the ability to invade tissue and survive in other parts of the body. Dysregulation of the protein TGF-β is known to drive breast cancer metastasis, but the precise molecular mechanisms are unknown. In this issue of the Journal of Clinical Investigation, researchers led by William Shiemann at Case Western Reserve University identified a microRNA, miR-181a, that is altered by TGF-β to promote metastasis. Shiemann and colleagues found that miR-181a repressed the expression of a protein, BIM1, which causes cells to die when they detach from surrounding tissue, a key step in metastasis. Additionally, they determined that increased expression of miR-181a was correlated with decreased overall survival in breast cancer patients. These findings suggest that miR-181a could potentially serve as a predictive marker for breast cancer metastasis.


TGF-β upregulates miR-181a expression to promote breast cancer metastasis

William Schiemann
Case Western Reserve University, Cleveland, OH, USA
Phone: 2163685763; Fax: 2163681166; E-mail: wps20@case.edu

View this article at: http://www.jci.org/articles/view/64946?key=70b36ab2304e923b57c3

Researchers identify rituximab-insensitive cells in patients with refractory thrombocytopenia purpura

Primary immune thrombocytopenia purpura (ITP) is a bleeding disorder in which the immune system generates antibodies that destroy platelets, the cells that cause blood to clot. B cells, immune cells that produce the antibodies that recognize the platelets, develop in the spleen. ITP patients are typically treated with rituximab, a drug that deplete B cells; however, many patients stop responding to this treatment and must have their spleens removed. In this issue of the Journal of Clinical Investigation, researchers led by Jean-Claude Weill and Claude-Agnès Reynaud at the Université Paris Descartes in Paris identified antibody-producing cells in the spleens of ITP patients that were not sensitive to B-cell depleting drugs. The development of these cells was promoted by rituximab treatment and provides an explanation for why some patients develop refractory ITP.


B-cell depletion in immune thrombocytopenia reveals splenic long-lived plasma cells

Jean-Claude Weill
Site Necker-Enfants Malades, Paris Descartes, Paris, , FRA
Phone: 00 33 1 40 61 53 80; E-mail: jean-claude.weill@inserm.fr

View this article at: http://www.jci.org/articles/view/65689?key=08e90fa6a89257a968dc

JCI Journals

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