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Northwestern Research Could Help Cancer Diagnoses

By Jessica Tobacman, Special to the Chicago Tribune

July 17, 2013

Northwestern University researchers contributed to a recent paper that contrasts the physical differences of normal and cancerous cells, research that could lead to more accurate diagnoses and evaluation of treatment.

"We found that cancer cells are much more flexible and adaptive, and can migrate greater distances without losing their integrity," said Thomas O'Halloran, principal investigator for the Physical Sciences-Oncology Center at Northwestern.

Researchers also found that there is increased disorder in the nuclei of the malignant cells and increased clumping in the cells' chromatin, or the combination of proteins and DNA in the nucleus of a cell, said Vadim Backman, biomedical engineering professor at Northwestern and senior author of the university's portion of the paper.

This clumping "makes it more difficult for the cell to fight cancer," and "advances the stages of the cancer," he said.

The mammoth, nationwide research effort includes experiments from 20 laboratories in 12 research centers, including Northwestern, the only Chicago-area representative. The centers together comprise a multidisciplinary Physical Sciences-Oncology Center network, which includes chemists, physicists, engineers, mathematicians, biologists and computational scientists.

"Everybody communicates and brings the techniques together," Backman said.

The paper, titled "A physical sciences network characterization of non-tumorigenic and metastatic cells," was published in the journal Scientific Reports in April.

Dhwanil Damania, who recently received his doctorate from Northwestern in biomedical engineering, and worked in Backman's laboratory, was the first author of the school's part of the overall paper; and Yolanda Stypula, who is a Ph.D. candidate in Backman's laboratory, was also an author of the publication.

The paper compared metastatic breast cancer cells to normal cells, using two of what are called "cell lines." A cell line is a cell culture with cells that have the same genetic makeup.

"This is a convenient way for scientists to study changes in the biology of cells," Backman said.

The Northwestern researchers used a technique developed in Backman's lab, called partial wave spectroscopic microscopy, or nanocytology, to study cell structure at a level of detail unavailable through a regular microscope.

Backman illustrated the differences between the methods by noting what would be visible through each when looking at a house after an earthquake. Although unable to see any problems in the building with a normal microscope, the nanocytology method allows scientists to look at the building's individual bricks and to see the cracks in those bricks.

In research terms, the cracks indicate which bricks, or cells, are predisposed to cancer.

"(Nanocytology) allows us to see the very first alterations in early cancer screening, to make early predictions of who will get cancer," Backman said. "It can improve the accuracy of cancer diagnoses, and help to assess the efficacy of treatment, since nano-changes happen so early in the process of treatment."

Cheryl Willman, director and CEO of the University of New Mexico Cancer Center, and professor in the departments of pathology and medicine at the university, called the study "interesting," and said that "they use some cool microscopic and imaging technologies." However, she also criticized the paper.

"The primary problem with this paper is that the authors have selected two cell lines that have crossed a critical experimental or laboratory barrier: They have been adapted to growing outside of the human body, ex vivo, for many years. Thus, how relevant these cell lines are to actual human cancers growing in the tumor microenvironment in vivo, in a human or in their body, is highly questionable," Willman said.

Backman affirmed Willman's critique of the study.

"This is a general concern with a cell line study," Backman said. "The point of the paper is to look at a cell line study to evaluate a variety of techniques on the same, well-controlled system."

Backman said Willman's criticism did not address the "point" of the article.

"The paper we're talking about does not discuss human data," Backman said. "The point of the paper is to look at physical changes in cancer cells. It is the most comprehensive analysis of the physical properties of cancer cells that has ever been done. When we complete the analysis, we can apply it to cells in humans.

"The goal is to test in human trials," he said.

Willman also said, "I would like to see them apply their studies to primary cancer cells, noncultured, which have undergone full genomic characterization or sequencing.

"In this way, they might begin to understand how cancer-causing mutations change cell behavior. That is actually the holy grail of today's cancer science. I don't think this work brings a lot of new insight into tumorigenesis or cancer invasion and metastasis in vivo."


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