JCI early table of contents for Aug. 6, 2012

August 06, 2012


Understanding colon cancer metastasis and invasion | Back to top

Chemokines are signals in the body that act as beacons, calling out to migrating cells, such as white blood cells, guiding them to where they are needed. One chemokine in particular, Chemokine 25 (CCL25), binds to Chemokine Receptor 9 (CCR9), forming a signaling pathway that is important in the small intestine and colon, where it regulates immune response and decreases cell death. Drs. Steven Lipkin, Xiling Shen, and colleagues at Cornell University have discovered that the CCL25-CCR9 pathway also has an unexpected role-- inhibiting colon cancer metastasis and invasion. They found that CCR9 was highly abundant in early stage colon cancer but surprisingly lacking in invasive and metastatic cancer, suggesting a role for this receptor in reducing the spread of colon cancer. By blocking this pathway in early stage cancer cells, they showed that tumor formation within the small intestine/colon was inhibited, but metastasis and invasion were increased. Furthermore, they found that activation of a second pathway called NOTCH, known to stimulate metastasis and invasion, promotes the degradation of CCR9, thus inhibiting the actions of its binding partner CCL25. This discovery sheds light on how colon cancer progresses and metastasizes.


Chemokine 25-induced signaling suppresses colon cancer invasion and metastasis


Steven Lipkin

Weill Cornell College of Medicine, New York, NY, USA

Phone: 2127747160; E-mail: stl2012@med.cornell.edu

View this article at: http://www.jci.org/articles/view/62110?key=ec3038b0ac205857d679


Identifying a new target for ALS treatment | Back to top

Amyotrophic lateral sclerosis (ALS) is a progressive disease wherein the cells of the central nervous system (CNS) involved in movement and coordination are destroyed. Although the mechanism of ALS is not completely understood, inflammation is believed to play a role in the disease process. A recent study by Howard Weiner and colleagues at Harvard Medical School and Tufts School of Medicine investigated the role of inflammation in a mouse model of ALS. Weiner and colleagues found that the recruitment of activated immune cells known as monocytes into the spinal cord correlated with increased CNS cell death, and this recruitment was mediated by high expression of the chemoattractant protein CCL2 by resident spinal cord-derived immune cells. Antibody-mediated depletion of the monocyte population reduced cellular recruitment to the spinal cord, decreased CNS cell death, and extended survival time in the mice. The analogous monocyte population in humans with ALS exhibited a similar inflammatory signature to the ALS model mice, suggesting that this cell population could serve as a marker of disease progression in human ALS patients. Thus, these results identify an inflammatory monocyte population as a potential therapeutic target for ALS.


Modulating inflammatory monocytes with a unique microRNA signature ameliorates murine ALS


Howard L. Weiner

Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA

Phone: 617-525-5300; Fax: 617-525-5252; E-mail: hweiner@rics.bwh.harvard.edu

View this article at: http://www.jci.org/articles/view/62636?key=c072141c367825b44d9b


Abnormal chromosome count may protect liver cells from injury | Back to top

The majority of liver cells contain an abnormal number of chromosomes, but these cells still retain their ability to divide. Researchers have long puzzled over why liver cells have unusual chromosome numbers, a state known as aneuploidy, and whether this genetic variation provides some benefit. To test whether aneuploidy protect liver cells agains liver injury, Andrew Duncan and colleagues at the University of Pittsburgh in Pennsylvania examined a mouse model of liver disease caused by deficiency of fumarylacetoacetate hydrolase (Fah). They knew that if these mice acquire a second mutation in proteins that regulate FAH, these mutations provide a selective advantage and protect from liver damage. To determine whether aneuploidy might contribute to these protective mutations, the Duncan team analyzed chromosomes from the mice. They found a striking prevalence in aneuploidy that lead to protective mutations in all mice that became completely resistant to liver injury. Their results suggest that the selection of a specific aneuploid mutations can result in the adaptation of liver cells to chronic liver injury.


Aneuploidy as a mechanism for stress-induced liver adaptation


Andrew Duncan

University of Pittsburgh, Pittsburgh, PA, USA

Phone: 412-624-5302; Fax: 412-624-5-5363; E-mail: duncana@pitt.edu

View this article at: http://www.jci.org/articles/view/64026?key=aa7f5f5ac5d39431b384


Natural killer T cells in adipose tissue prevent insulin resistance | Back to top

A high fat diet can lead to lipid overload and disfunction of fat cells (adipocytes), which can eventually lead to insulin resistance. A specialized population of immune cells known as invariant natural killer T cells (iNKT cells) have been proposed to contribute to lipid overload and insulin resistance in response to high fat diet, but the role of these cells in insulin resistance remains somewhat unclear. Dr. Marianne Boes and colleagues at UMC Utrecht in the Netherlands sought to examine the role of iNKT cells in insulin resistance in the absence of a high fat diet. They found that low fat diet-fed mice lacking iNKT cells displayed insulin resistance, but showed no obvious evidence of adipose tissue inflammation. However, these mice were characterized by an increase in the proliferation of adipocytes and dysregulated levels of the endocrine hormones leptin and adiponectin. Their data supports that iNKT cells in adipose tissue promote healthy tissue through direct crosstalk with adipocytes.


Natural killer T cells in adipose tissue prevent insulin resistance


Marianne Boes

UMC Utrecht, Utrecht, , NLD

Phone: +31633089284; E-mail: mboes@umcutrecht.nl

View this article at: http://www.jci.org/articles/view/62739?key=733445fe8021b9a60221

JCI Journals

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