Reducing breast cancer metastasis

In a step toward finding new treatments for metastatic breast cancer, researchers reported that inhibiting an enzyme called LOXL2 leads to reduced metastasis of cancer in mouse models of breast cancer. The enzyme LOXL2, or lysyl oxidase–like 2, is a member of the LOX family of extracellular matrix–modifying enzymes, all of which are implicated in cancer progression.

Janine Erler of The Institute of Cancer Research in London and colleagues analyzed previously published data from human breast cancer biopsies and found that LOXL2 expression was significantly correlated with decreased overall survival and decreased metastasis-free survival. Analyses in mouse models of breast cancer revealed that LOXL2 is not required for primary tumor growth, but that it does enable metastases (Cancer Res. 71, 1561–1572; 2011). The team administered an antibiotic that inhibits LOXL2 to mice engineered to develop cancer and found that the treated mice had significantly fewer lung metastases than did the control mice.

The researchers note that their results suggest that LOXL2 inhibitor should be considered for the development of new metastatic breast cancer therapies. Additionally, these results raise “the possibility that we could develop a test to measure LOXL2 levels and predict [which patients] will develop aggressive disease,” Holly Barker, a coauthor, said in a press release.

Mending damaged hearts

Some fish and amphibians can repair damaged cardiac tissue throughout life. Now, researchers have shown that newborn mice can also recover lost heart muscle tissue, in a manner that appears to be similar to how zebrafish repair damaged heart tissue. Within one week after birth, however, mice lose this regenerative ability.

Hesham Sadek of the University of Texas Southwestern Medical Center in Dallas and colleagues removed about 15% of muscle tissue in the ventricular walls of one-day-old mice (Science 331, 1078–1080; 2011). The authors observed signs of heart muscle cell proliferation in the heart at one week after the surgery. Within three weeks of the operation, the animals had fully recovered muscle tissue and within two months, the left ventricle was pumping blood normally again. When they carried out a similar surgery on seven-day-old mice, the authors observed no cardiomyocyte proliferation at one week after the surgery.

Adult mammalian hearts are able to regenerate some damaged heart muscle, but not quickly enough to sufficiently repair a heart after a major injury. The team is now looking for genes, gene silencers and drugs that could help the adult heart regain this regenerative potential, Eric Olsen, a coauthor of the paper, told Nature.

Histamine links allergy and autoimmune disease

The neurotransmitter histamine is known to be involved in allergic reactions and other physiological processes. It works by dilating blood vessels and making their walls more permeable so that immune cells can move around more easily. To the extent that autoimmune disorders share some characteristics with allergic reactions, it seems reasonable that similar pathways could be involved in both processes. Now, new research shows that histamine and its receptors may ameliorate disease effects and pathology in mice with experimental autoimmune encephalomyelitis (EAE), an animal model of the human autoimmune syndrome multiple sclerosis (MS), which has no known cure.

The study group, led by Rosetta Pedotti (IRCSS Carlo Besta, Milan, Italy), found that histamine and histamine receptors inhibited the development of EAE in two ways. First, they inhibited proliferation and production of interferon-γ of T cells that had been activated to cause EAE. Second, they inhibited the ability of these myelin-autoreactive T cells to adhere to brain blood vessels and cross the blood–brain barrier (J. Leukocyte Biol. 89, 259–267; 2011).

Because these processes are both crucial in the development of MS, the authors conclude that histamine may have therapeutic potential for MS in humans but caution that further investigation is needed.