December 12, 2008

Aliquots — Research highlights from VUMC laboratories

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Markers predict prostate cancer return

Prostate cancer is the second leading cause of cancer deaths in men. Yet, it is often over-treated since clinical features provide low specificity in predicting those cancers likely to metastasize. Distinguishing patients likely to develop aggressive cancers – and thus might benefit from more aggressive therapy – has been a major hurdle.

Because inflammatory molecules called chemokines have been implicated in prostate cancer progression, Neil Bhowmick, Ph.D., and colleagues examined whether chemokine expression in surgically removed prostate tissue could predict biochemical recurrence – an elevation of prostate specific antigen (PSA) – within five years of prostatectomy.

In the Dec. 1 issue of Clinical Cancer Research, the researchers identify two chemokines – CX3CL1 and IL-15 – whose expression was associated with recurrence-free survival and another – CCL4 – whose expression was associated with biochemical recurrence. Combining these markers with established clinical variables was a better predictor of recurrence than using clinical features alone. The results could provide clinicians with a strategy to identify patients most likely to benefit from secondary treatment following prostatectomy.

Melissa Marino


‘Superhealer’ mice give repair advice

Bone marrow-derived mesenchymal stem cells (MSCs) offer promise as a cell therapy for heart and wound regeneration. But the molecular pathways that regulate MSC function – and that might be modulated to enhance their therapeutic potential – are poorly understood.

Pampee Young, M.D., Ph.D., and colleagues compared MSCs from control and “superhealer” mice – a strain called MRL that is known to have enhanced tissue regeneration. They showed that MRL-MSCs outperformed control MSCs in mouse tissue repair and heart attack models. Gene expression analysis of the two types of MSCs revealed increased expression of inhibitors of the Wnt signaling pathway (called sFRPs) in the MRL-MSCs. They found that reducing sFRP2 expression in MRL-MSCs decreased their regenerative capacity, and that increasing sFRP2 levels in control MSCs conferred “superhealer” powers on these cells.

The findings, reported in the Nov. 25 Proceedings of the National Academy of Sciences, implicate sFRP2 in MSC regenerative potential and could lead to improved cell therapies for heart and wound repair.

Leigh MacMillan


Molecular gut check

Intestinal intraepithelial lymphocytes (IEL) are gut immune cells that respond to both pathogenic and beneficial gut microbes. These cells exist in a state of “partial activation,” which makes them capable of initiating a rapid immune response. But to avoid unwanted reactions – like those underlying inflammatory bowel diseases – they must be held in check.

Luc Van Kaer, Ph.D., and colleagues proposed that the thymus leukemia (TL) antigen – a molecule expressed specifically in gut cells – regulates IEL function. To test this, the researchers generated mice lacking TL and found that these mice had enhanced immune responses in the gut. When TL-deficient mice were bred to another strain susceptible to inflammatory bowel disease, the resulting offspring showed a more severe and rapid onset of inflammatory responses than the mice lacking TL alone.

The findings, reported in the Nov. 18 Proceedings of the National Academy of Sciences, indicate an important role for TL in controlling gut immune responses and suggest a potential new therapeutic target for inflammatory bowel diseases.

Melissa Marino


Egg-ripening factor

Meiosis – the cell division process that gives rise to sperm and eggs – must be carefully regulated to prevent chromosomal mishaps. The molecular factors that control the timing of egg meiotic maturation are unclear.

Jessica Von Stetina, Ph.D., Daniela Drummond-Barbosa, Ph.D., and colleagues have identified a novel role for a protein called alpha-endosulfine in fruit fly egg maturation. They report in the Nov. 15 issue of Development that eggs from fruit flies with mutant alpha-endosulfine stall during meiosis and fail to mature (they previously showed that these mutant flies are infertile).

The investigators propose that alpha-endosulfine controls meiotic maturation by regulating the actions of other proteins involved in cell division (Twine, Polo and Elgi). They also show that expression of the human alpha-endosulfine gene in the mutant flies rescues the meiotic and fertility defects and that alpha-endosulfine is expressed in mouse ovaries, suggesting that its function in egg meiotic maturation may be conserved.

Leigh MacMillan


We welcome suggestions for research to highlight in Aliquots. The items should be primary research articles (no reviews, editorials or commentaries) published within the last two months in a peer-reviewed journal. Please send the article citation (PDF if available) and any other feedback about the column to:


Past Aliquots

June 22, 2012
June 8, 2012
May 11, 2012
April 27, 2012
April 13, 2012
March 30, 2012
March 16, 2012