Researchers Track Changes in Blood Protein Levels During Breast Cancer Development

Cancer researchers have identified a set of proteins in the blood that change in abundance during tumor development, a process that begins long before the cancer is clinically detectable.

Investigators at the Fred Hutchinson Cancer Research Center (Seattle, WA, USA) worked with the conditional transgenic neu-induced mouse model of breast cancer to determine the extent and source of changes in the plasma proteome at predetermined stages of tumor development. The neu is an activated rat homologue of the human epidermal growth factor receptor 2 (ErbB2) gene. ErbB2 is a receptor tyrosine kinase amplified and overexpressed in more than 25% of human breast cancers, and signaling from this oncogene is a central driver in breast cancer development.

When induced with doxycycline, the mice population synchronously develops invasive breast tumors that recapitulate the morphologic, pathologic, and molecular features of ErbB2-positive human breast cancer. In contrast, doxycycline withdrawal results in transgene de-induction and tumor regression, mimicking responses of tumors to targeted therapy.

The investigators used mass spectrometry to analyze blood proteins at different stages of cancer development in the mouse model system. They reported in the August 1, 2011, online edition of the journal Cancer Research that approximately 500 different proteins were detected, and that up to a third of these changed in abundance; the number increased with cancer growth and decreased with tumor regression.

“We found a treasure trove of proteins that are involved in a variety of mechanisms related to cancer development, from the formation of blood vessels that feed tumors to signatures of early cancer spread, or metastasis,” said senior author Dr. Christopher J. Kemp, a researcher at the Fred Hutchinson Cancer Research Center. “The overall surprising thing we found was the degree to which the host responds to cancer early in the course of disease progression, and the extent of that response. While a mouse - or presumably a human - with early-stage cancer may appear normal, our study shows that there are many changes occurring long before the disease can be detected clinically. This gives us hope that we should be able to identify those changes and use them as early detection tools with the ultimate goal of more effective intervention.”

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Fred Hutchinson Cancer Research Center