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Key enzyme in breast cancer development identified (updated)

[UPDATE: This entry has been modified to include the name of the lead author of the study and to explain how the study relates to earlier research at Stanford that implicated LOX in tumor metastasis.]

A team of sScientists from the United States and United Kingdom have pinpointed an enzyme crucial for turning abnormal but non-malignant breast tissue into tumors by stiffening the tissue, according to a study published online in the journal Cell. The study was led by Valerie Weaver, PhD, at the University of California, San Francisco.

In a study involving mice, researchers discovered higher levels of an enzyme called lysyl oxidase (LOX) increased the levels of collagen in mammary glands, made the tissue stiffer and correlated with a higher frequency of tumors invading the breast tissue. Scientists also found using chemicals or an antibody to block LOX reduced the chances of tumors forming, and increased the likelihood that when they did develop, they were smaller and less aggressive.

Co-author Janine Erler, PhD, who contributed to the project while at Stanford and is now at The Institute of Cancer Research in England, explained in a release how the research could make cancer treatments more effective:

The enzyme triggers a clear physical change in breast tissue and, if we could stop this happening, we expect it would slow the growth of any cancers that did develop and make them easier to eradicate.

The scientific breakthrough builds on pPrevious studies completed at the Stanford School of Medicine in Amato Giaccia's laboratory focused on LOX. In their research, Giaccia and his team highlighted the importance of LOX in cancer spread, showing that it promotes metastasis by sending out signals that prepare a new area of the body for invasion.

In contrast to those earlier studies, the current work emphasizes the critical role of early changes in the tissue microenvironment induced by LOX. The study results build upon earlier work conducted by Weaver and colleagues that implicated integrins (receptors that help mediate attachment between a cell and surrounding tissue) as signaling molecules that play an important role in directing the cancerous behavior of a tissue. The findings also suggest why human tumors that are typically stiffer than normal tissue so often have high integrin activity.

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