Three-dimensional images of single cells can be used to pick out telling differences between malignant breast cancer, benign tumors, and normal cells. Researchers at Arizona State University in Phoenix hope that this imaging technology will help provide more accurate diagnosis and staging of cancers.

Led by Deirdre Meldrum, PhD, director of the Center for Biosignatures Discovery Automation in Arizona State's Biodesign Institute, the researchers characterized the nuclei of breast cancer cells using a 3-dimensional light microscope created by VisionGate, Inc., of Phoenix, AZ (PloS One 2012;7:e29230).

Meldrum and colleagues prepared samples of 3 types of human breast epithelial cell lines: normal, benign fibrocystic, and malignant. VisionGate has developed a way of treating cells so that they maintain their normal architecture, instead of placing them on glass slides that encourage the cells to flatten out. The cells are flowed through a capillary and then held in place while the capillary rotates so that the microscope can capture hundreds of 2-dimensional images of each cell from different angles, much like a computed tomography scanner. These images are then processed and combined to make a 3-dimensional image.

Three-dimensional microscopy can derive a biosignature for normal, benign fibrocystic, and breast cancer cells. The top row shows a normal breast epithelial cell with the nucleus (in blue) having a smooth membrane of regular shape. The bottom row shows a metastatic breast cancer cell with multilobular nuclear morphology. The left column exhibits the whole cell, and the right column shows intranuclear density variations (increasing from blue to red). [Photo courtesy of Arizona State University]
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Three-dimensional microscopy can derive a biosignature for normal, benign fibrocystic, and breast cancer cells. The top row shows a normal breast epithelial cell with the nucleus (in blue) having a smooth membrane of regular shape. The bottom row shows a metastatic breast cancer cell with multilobular nuclear morphology. The left column exhibits the whole cell, and the right column shows intranuclear density variations (increasing from blue to red). [Photo courtesy of Arizona State University]

Three-dimensional microscopy can derive a biosignature for normal, benign fibrocystic, and breast cancer cells. The top row shows a normal breast epithelial cell with the nucleus (in blue) having a smooth membrane of regular shape. The bottom row shows a metastatic breast cancer cell with multilobular nuclear morphology. The left column exhibits the whole cell, and the right column shows intranuclear density variations (increasing from blue to red). [Photo courtesy of Arizona State University]
View largeDownload slide

Three-dimensional microscopy can derive a biosignature for normal, benign fibrocystic, and breast cancer cells. The top row shows a normal breast epithelial cell with the nucleus (in blue) having a smooth membrane of regular shape. The bottom row shows a metastatic breast cancer cell with multilobular nuclear morphology. The left column exhibits the whole cell, and the right column shows intranuclear density variations (increasing from blue to red). [Photo courtesy of Arizona State University]

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The Arizona group focused on the cell nucleus, which pathologists have long used as a hallmark for diagnosing and staging cancer. “We showed we can derive a biosignature for normal cells, benign ones, and breast cancer cells, based on shape and texture measurements,” says Roger Johnson, PhD, research laboratory manager at the Center. The group came up with about 50 nuclear features that can be used to distinguish the 3 cell types.

“Little is known about the nucleus,” comments John Sedat, PhD, a professor of biophysics at the University of California, San Francisco, who studies the nucleus via imaging. “Three-dimensional data provide a different wrinkle, which is good.” However, he notes that patient data are likely to present a more complex picture than one would get from cell lines adapted to thrive in the lab.

For more news on cancer research, visit Cancer Discovery online at www.AACR.org/CDnews.

©2012 American Association for Cancer Research.
2012