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Tissue Tension Regulates Tumor Progression

By Elizabeth Fernandez, UCSF News Office | November 20, 2009

UCSF scientists have shown for the first time that the rigidity of a tissue can induce cancer. The research team identified an enzyme that is crucial for regulating tissue stiffness and demonstrated that the enzyme can turn abnormal but non-malignant breast tissue into tumors, according to a study published in "Cell" online.

Blocking the enzyme lysyl oxidase (LOX) decreased tissue stiffness and reduced the chance a tumor would form. It also caused tumors that did develop to be smaller and less aggressive, said senior author Valerie Weaver, PhD, associate professor and director of the Center for Bioengineering and Tissue Regeneration in the Department of Surgery at the University of California, San Francisco.

Study findings appear online at http://www.cell.com/abstract/S0092-8674(09)01353-1.

"Our study shows how stiffening of the breast tissue that is controlled by enzymes such as LOX is a key process that regulates cancer development,'' said Weaver. "These findings suggest that any factor that increases the stiffness in a tissue could promote cancer. The most compelling finding of the study is that the research team identified enzymes that regulate tissue stiffening -- opening up the possibility for the development of targeted therapies. The enzyme triggers a clear physical change in breast tissue and, if we could stop this happening, we expect it would prevent cancers from progressing and hopefully also prevent tumor metastasis which is the leading cause of patient mortality.''

The supportive tissue surrounding cancer cells is shaped differently than healthy tissue and is stiffer and more fibrous. These properties help doctors detect breast cancers, but until now scientists have not appreciated that these physical changes actually control tumor development and no one has yet identified factors that regulate these modifications, according to Weaver, who is affiliated with the UCSF Helen Diller Family Comprehensive Cancer Center and the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF. She is also an associate professor in the Department of Anatomy and the new Department of Bioengineering and Therapeutic Sciences at UCSF.

Read more at Elizabeth Fernandez, UCSF News Office