Attacking “bad carbs” to fight ovarian cancer

By Ana Miletic Sedy
January 20, 2012

Carbohydrates are not only found in many of the foods that we love to eat (think bread and pasta), they also coat the surfaces of all cells in the body. What’s more, when a healthy cell becomes a cancer cell, the surface carbohydrates (also known as glycoproteins) are sometimes altered in a way that can contribute to tumor growth and metastasis.

Glycobiology, the study of glycoproteins and their role in human health, is a relatively underappreciated scientific field. But identifying cancer cell glycoproteins and understanding their part in cancer is a focus of Michiko Fukuda, Ph.D.’s laboratory. As she puts it, “Many people don’t want to think a lot about carbohydrates.”

Recently, two postdoctoral researchers who work with Fukuda, Toshiaki Shibata, M.D. and Fumiko Matsumura, Ph.D., identified a glycoprotein that is expressed on malignant ovarian cancer cells. Their findings, and the new biochemical method pioneered in the course of their research, were published December 22 in the Journal of Biological Chemistry. This work was so significant, in fact, that the journal’s editors selected the work as “Paper of the Week,” making it one of the top one percent of papers published by the journal.

Here’s what they did: Fukuda, Shibata, Matsumura, and colleagues were interested in an antibody that binds to ovarian cancer cells, but they didn’t know the identity of the glycoprotein that the antibody recognized. Instead of taking a trial-and-error approach to find the binding partner for this antibody, scientists in the Fukuda laboratory pioneered a novel genetic approach. They expressed a large collection of genes that make different cell surface-expressed carbohydrates in cells. Then they took away the genes one-by-one and looked for the loss of antibody binding on the surface of the cells. Knowing the type of carbohydrates that the missing genes make allowed the researchers to work backwards and identify the carbohydrates expressed on the malignant ovarian cancer cells.

New therapies for ovarian cancer are badly needed. With a survival rate of only 47 percent, ovarian cancer is the second most common gynecologic cancer and was the cause of nearly 14,000 deaths in the United States in 2010. In this regard, the glycoprotein identified by the Fukuda laboratory represents an important potential target for cancer therapy as it has been suggested it plays a role in metastasis of ovarian cancer. According to Fukuda, the next step is to use a small inhibitor to see if blocking the ability of the identified ovarian cancer glycoprotein to bind to the body’s cells can block the spread of ovarian cancer.

“We are pioneers of carbohydrates in metastasis,” said Fukuda, who also credited the environment at Sanford-Burnham as being instrumental for the success of their research. “Most people don’t have the resources that we have here at this institute.”

Original paper:
Shibata TK, Matsumura F, Wang P, Yu S, Chou CC, Khoo KH, Kitayama K, Akama TO, Sugihara K, Kanayama N, Kojima-Aikawa K, Seeberger PH, Fukuda M, Suzuki A, Aoki D, & Fukuda MN (2011). Identification of mono- and di-sulfated N-acetyl-lactosaminyl oligosaccharide structures as epitopes specifically recognized by humanized monoclonal antibody HMOCC-1 raised against ovarian cancer. The Journal of biological chemistry PMID: 22194598

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