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Rare Variant of Mucin, MM, Marks Differentiated yet Tumorigenic and Invasive Breast Cancer Cells





A Berkeley Lab research team led by Mina Bissell and her Danish collaborator, Dr. Ole Petersen, has discovered a biological marker that may be used to predict whether certain kinds of breast cancer cells have the ability to become more aggressive, invasive, or metastatic. Surprisingly, this marker is present on differentiated cells, not stem cells.
The research team found that breast cancer cells that carry surface receptor p75NTR have many of the characteristics of breast cancer stem cells, including tumorigenicity and invasiveness. At least one type of differentiated progeny of the p75NTR cells was even more tumorigenic and invasive than progenitors. This subpopulation of potentially aggressive, differentiated breast cancer cells can be identified by a distinctive cell-surface carbohydrate structure, Gal b(1-4) GlcNc b(1-6), or MM. MM is a minor subtype of the glycans known as mucins. Analyses of clinical samples from women with breast cancer revealed that the presence of MM+ cells, independent of breast cancer subtype, marks invasive, aggressive breast cancers with a poor prognosis.

An antibody assay to detect MM+ cells could be an effective breast cancer diagnostic, identifying patients with a poor prognosis who might benefit from more aggressive breast cancer therapies. Standard gene expression tests cannot currently identify this particular subtype because the MM marker is a post-translational modification of the carbohydrate moiety of mucin molecules. Patients who do not carry the MM marker, whose cancers therefore are less likely to progress, could benefit from less aggressive treatment and monitoring.

The MM marker might also be used as a cell-surface target for precision therapeutics designed to kill this particular subpopulation of cancer cells. When combined with companion drugs that similarly target other subpopulations, these novel therapeutic combinations could destroy the most dangerous subtypes of cells while leaving healthy or benign breast cells unharmed.

DEVELOPMENT STAGE: Proven principle

STATUS:  Patent pending.  Available for licensing or collaborative research.

Kim, J., Villadsen, R., Sørlie, T., Fogh, L., Grønlund, S.Z., Fridriksdottir, A.J., Kuhn. I., Rank, F., Wielenga, V.T., Solvang, H., Edwards, P.A.W., Børresen-Dale, A.-L., Rønnov-Jessen, L., Bissell, M.J., Petersen, O.W., “Tumor initiating but differentiated luminal-like breast cancer cells are highly invasive in the absence of basal-like activity,” PNAS, Vol. 109, no. 16, 6124-6129, April 17, 2012.


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Last updated: 09/16/2013