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Hyaluronan-based Probes for Identification of Invasive Breast Cancer Subsets

IB-2894

APPLICATIONS OF TECHNOLOGY:

ADVANTAGES:

ABSTRACT:

A research team led by Mina Bissell and Mandana Veiseh of Berkeley Lab and Eva Turley of London Health Sciences Centre, London, Ontario has developed a novel system for assessing the aggressiveness of breast cancer by using a probe that identifies cells with increased metabolism of hyaluronan (HA), a complex natural sugar polymer active in both normal wound healing and tumorigenesis. The team discovered that HA was a marker for poorly proliferative but highly invasive cancer subsets and could be used to sort that particular invasive tumor cell types from less harmful ones.

Studies by the team have shown that formulations of HA can be safely injected in human subjects and are well tolerated. Accumulations of HA in aggressive cancerous tissues grown in immune-compromised animals as well as sites of tissue injury can be imaged in vivo when fluorescent or other imaging contrast agents (such as nuclear or magnetic resonance) are attached to the sugar molecule. The detectable increased accumulation of HA and expression of CD44 and RHAMM identify subsets of invasive cell types that may serve as prognostic indicators of poor outcome in breast cancer.

As such, the HA-based probe can be used effectively to sort patients needing invasive therapies from those who do not. As a therapeutic extension of this finding, the target binding capacity of these HA-based probes may be exploited to target chemotherapy or toxic agents directly to the site of the invasive tumor tissue. That is, these HA-based agents can function as “theranostics,” in which cancer treatments are tailored for delivery to the tissue type of individual patients, while the results of that intervention are simultaneously assessed by the diagnostic component.

Increases in HA synthesis, cellular uptake, and metabolism occur during the remodeling of tissue microenvironments following injury or during growth of cancerous masses. In particular, HA binds with cell surface receptors CD44 and RHAMM, which are known to form complexes with signaling enzyme ERK1,2 that promote the motility associated with invasive cancer cells.

DEVELOPMENT STAGE:  Bench scale prototype.

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

FOR MORE INFORMATION:

Veiseh, M., Breadner, D., Ma, J., Akentieva, N., Savani, R.C., Harrison, R., Mikilus, D., Collis, L., Gustafson, S., Lee, T.Y., Koropatnick, J., Luyt, L.G., Bissell, M.J., Turley, E.A., “Imaging of Homeostatic, Neoplastic, and Injured Tissues by HA-Based Probes,” Biomacromolecules, 2012, Vol. 13, No. 1, pp. 12-22.

Veiseh, M., Turley, E.A., “Hyaluronan metabolism in remodeling extracellular matrix: probes for imaging and therapy of breast cancer,” Integrative Biology, 2011, Vol 3, pp 304-315.

Hamilton, S.R., Veiseh, M., Tölg, C., Tirona, R., Richardson, J., Brown, R., Gonzalez, M., Vanzieleghem, M., Anderson, P., Asculai, S., Winnik, F., Savani, R., Freeman, D., Luyt, L., Koropatnick, J., Turley, E.A., “Pharmacokinetics and Pharmacodynamics of Hyaluronan Infused into Healthy Human Volunteers,” The Open Drug Metabolism Journal, 2009, Vol. 3, pp. 44-55.

SEE THESE OTHER BERKELEY LAB TECHNOLOGIES IN THIS FIELD:

Early Detection of Metastatic Cancer Progenitor Cells, JIB-2006

Biomarkers for Predicting Breast Cancer Patient Response to PARP Inhibitors, JIB-3095

REFERENCE NUMBER: IB-2894

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Last updated: 03/08/2013