Metastasis-Promoting Protein Identified; Could Provide a Prognostic Test Or Target for Breast Cancer

	Tweet

Tumors that are about to progress and metastasize go through a process also seen in normal embryonic development, known as the epithelial to mesenchymal transition (EMT). Tumor cells revert to a less-differentiated state, stop adhering to each another and become more mobile and prone to invade and proliferate. Now, researchers at Children’s Hospital Boston show, for the first time, that a small protein called lipocalin 2 triggers the EMT in human breast cancer – and that the same protein, when measured in tissues and urine, can predict a cancer’s invasiveness. Their findings were published online February 23 by the Proceedings of the National Academy of Sciences.

Researchers led by Marsha A. Moses, PhD, and Jiang Yang, PhD, of the Vascular Biology Program at Children’s, induced human breast cancer cells to make large amounts of lipocalin 2, and showed that cell motility and invasiveness increased significantly. They then took cells from aggressive breast cancers and silenced lipocalin 2, and found that cell migration was significantly inhibited. When they transplanted human breast cancer cells into animals, those from tumors making lipocalin 2 were more locally invasive and more likely to metastasize to lymph nodes.

Further laboratory studies indicated that lipocalin 2 decreases the levels of estrogen receptor alpha, thereby reducing the cells’ response to the hormone estrogen, which is associated with poor prognosis of breast cancer. Inhibiting the production of estrogen receptor alpha is also the mechanism that triggers the EMT pathway, the researchers show.

Finally, tissue samples, and even urine samples, from women with invasive breast cancer consistently showed elevated lipocalin 2 levels, suggesting that testing for lipocalin 2 may be a way of detecting cancer progression and the need for more aggressive treatment.

“Our study identifies a novel, additional player in the complex development of invasive breast cancer,” says Moses, the Vascular Biology Program’s interim director. “It suggests that this protein may represent a prognostic and/or therapeutic target for this devastating disease.”

Lipocalin 2, along with other urine biomarkers of cancer identified in Moses’s lab, has been licensed to Predictive Biosciences, Inc. (Lexington, Mass.) for clinical development.

The study was funded by the National Institutes of Health, the JoAnn Webb Fund for Angiogenesis Research, the Riehl Family Foundation, the S. Elizabeth O’Brien Trust and the Advanced Medical Foundation.

Children’s Hospital Boston is home to the world’s largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 500 scientists, including eight members of the National Academy of Sciences, 11 members of the Institute of Medicine and 13 members of the Howard Hughes Medical Institute comprise Children’s research community. Founded as a 20-bed hospital for children, Children’s Hospital Boston today is a 397-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Children’s also is the primary pediatric teaching affiliate of Harvard Medical School.

Source: Children’s Hospital Boston

RELATED STORIES:
Reconstruction surgery rarely discussed with breast cancer patients   Cancer study backs Herceptin with chemo   Scott & White Healthcare pathologist is co-investigator on breast cancer study   Princeton scientists discover mechanism involved in breast cancer’s spread to bone   Breast Cancer Not Just a Woman’s Disease   Diet may lower breast cancer risk before menopause   City-dwelling women at greater risk for breast cancer   Should You Have a Mastectomy to Prevent Breast Cancer?   Breast cancer and heart disease may have common roots   Removing 2mm around breast cancer tumors prevents residual disease in 98 percent of patients   One in Five Breast Cancer Patients May Not Adhere to Hormone Therapy   Different Gene-Expression Predictors of Breast Cancer Agree   Statin Therapy Ineffective in Breast Cancer Prevention   Risk of breast cancer mutations underestimated for Asian women, Stanford study shows   Breast cancer patients with BRCA gene diagnosed almost 8 years earlier than generation before   Women not following through with recommended breast screening MRI   New national poll: 89 percent of women said mammograms vital to their health   Breast Density Linked to Increased Risk of Subsequent Breast Cancer   High insulin levels raise risk of breast cancer in postmenopausal women   Study helps eliminate causes for joint pain linked to commonly used breast cancer drugs   Whites take supplemental breast cancer therapy more often than blacks   Enhanced DNA-repair mechanism can cause breast cancer

Comments

[ + Post Your Own ]

Now you're in the public comment zone. What follows is not Armenian Medical Network's stuff; it comes from other people and we don't vouch for it. A reminder: By using this Web site you agree to accept our Terms of Service. Click here to read the Rules of Engagement.

There are no comments for this entry yet. [ + Comment here + ]