September 4, 2009

Aliquots — research highlights from VUMC laboratories


Breast cancer bone breakdown

Bone metastasis is common in breast cancer. Cancer cells hijack the normal bone growth process, abnormally activating osteoclasts – the cells involved in bone destruction (osteolysis) – and releasing growth factors that promote tumor survival. This results in a vicious cycle of tumor-induced osteolysis.

Matrix metalloproteinase enzymes are highly expressed in the tumor-bone microenvironment. Two of these, MMP-7 and MMP-9, are localized in osteoclasts, but their roles in osteolysis are unclear.

Using mouse models, Conor Lynch, Ph.D., and colleagues found that MMP-7 significantly contributes to tumor-induced osteolysis. MMP-9 had no effect. The investigators also found that levels of RANKL – a mediator of osteoclast recruitment and maturation – were lower in MMP-7 null mice compared to wild-type controls. The results reported in the Aug. 15 issue of Cancer Research suggest that inhibiting MMP-7 in the tumor environment could improve treatment of breast-to-bone metastases.

Leslie Hast


No easy breathing with fish oil

Increased dietary intake of fish oil, with its “healthy” omega-3 fatty acids, may be associated with a reduced risk of asthma, but clinical studies of this intervention have had ambiguous results.

Huiyong Yin, Ph.D., and colleagues used a mouse model of allergic lung inflammation to study the effects of fish oil supplementation on airway inflammation. They found that allergic challenge caused an increase in the levels of F2-isoprostanes, a measure of oxidative stress, which is thought to play a role in the pathophysiology of asthma.

Fish oil supplementation reduced the levels of F2-isoprostanes, but the levels of other isoprostanes (F3- and F4-), derived from the omega-3 fatty acids, increased. Fish oil enhanced the production of pro-inflammatory cytokines (IL-5 and IL-13) in the lung and suppressed production of the lung-protecting molecule PGE2.

The findings, reported in the Sept. 1 issue of Free Radical Biology & Medicine, bring into question the role of fish oil supplementation in the treatment of asthma.

Leigh MacMillan


Compounds offer cognitive boost

Drugs capable of enhancing cognitive function have a wide variety of potential applications, including treatment of cognitive deficits in schizophrenia. The neurotransmitter glutamate plays a key role in the physiological processes – long-term potentiation (LTP) and long-term depression (LTD) – that underlie learning and memory.

Jeffrey Conn, Ph.D., and colleagues have developed positive allosteric modulators (PAMs) of the metabotropic glutamate receptor, mGluR5, which “turn up” the normal activity of the receptor when glutamate binds. These highly selective PAMs have shown potential in alleviating the positive symptoms of schizophrenia (e.g., hallucinations), but their impact on cognitive function was not clear.

In the August issue of Neuropsychopharmacology, the researchers show that mGluR5 PAMs enhance both LTP and LTD but do not alter the balance or patterns of activity. The compounds also enhanced performance in a spatial learning and memory task in mice. The findings suggest that these agents may provide a novel approach for treating impaired cognitive function.

Melissa Marino


Found: cell responders to RSV

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis (inflammation of the lung’s tiniest air passages) and viral pneumonia in infants worldwide. It sends more than 100,000 babies to the hospital each year in the United States.

In mouse models of RSV infection, the immune system signaling protein interleukin-4 (IL-4) contributes to the pathology of the disease, but the cellular source of IL-4 is unknown. Martin Moore, Ph.D., Stokes Peebles, M.D., and colleagues investigated the role of IL-4 in RSV infection in two mouse models.

The findings in the Aug. 1 Journal of Immunology provide new insights and implicate an unexpected cell population in the pathogenesis of RSV-mediated disease.

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