Yale Bulletin and Calendar

October 3, 2003|Volume 32, Number 5

Team learns sugars produced by
cancers may help disease spread

Yale researchers have found that as many as 22 kinds of cancers produce abnormal sugars that might help metastasize or spread the disease throughout the body, a discovery that may lead to new drug targets.

The study, published in the September issue of Cancer Research, showed that the presence of these sugars, called "branched oligosaccharides," are associated with structures called autophagosomes, part of the cellular digestive system. The findings show that this is a common and pervasive trait of melanomas and a wide variety of other cancers, including those of the lung, colon, breast, prostate, kidney and lymphatic system.

Previous laboratory and animal studies showed that the sugars and the enzyme that produces them are associated with metastasis (cancer growth), but there was little information on the actual abundance and distribution of the sugars in human tumors. The sugars are normally associated with certain white blood cells and are used by these cells and cancer cells alike to move throughout the body.

"That they were most abundant on metastases is particularly encouraging, because locating and killing metastatic cancer cells is the most difficult aspect of cancer therapy," says John Pawelek, senior research scientist at the School of Medicine, who co-authored the study with Dr. Tamara Handerson of Tufts University School of Medicine. "Our lab has initiated some projects in this regard, and we are excited that at least under experimental conditions, the sugars can indeed be exploited as signals for targeting and destroying human cancer cells."

Pawelek says that although the sugars were seen in other areas of the cancer cell, they were always found associated with autophagosomes, which come in all sizes and function in the cellular digestive system.

"We don't understand the significance of these structures to cancer," says Pawelek. "That they are a common trait of most cancers wasn't noticed before, probably because they are not visible to pathologists unless special tissue stains were used. Autophagosomes were readily visible with a staining technique called lectin histochemistry because they were coated with the sugars.

Nearly 90% of more than 300 metastic breast cancers examined expressed the sugars and autophagosomes in abundance. Along with two colleagues in Yale's Department of Pathology -- Dr. Robert Camp and Dr. David Rimm -- Pawelek and Handerson have determined that expression of this trait in primary breast cancer tumors is a high-risk factor and predictive of poor patient prognosis.

Pawelek says the study also unexpectedly provided an explanation for the well-known hyperpigmented or dark areas of primary melanomas, used by dermatologists in the clinical diagnosis of melanoma of the skin. Handerson and Pawelek found that these areas were darker because they contained cells rich in autophagosomes and the abnormal branched oligosaccharides.

"In the case of melanoma, the autophagosomes were often filled with melanin, so we could see them without any other stains," says Pawelek. "Curiously, these cells tended to make more melanin than normal pigment cells, hence the dark areas of
the tumors."

Now that the initial results have emerged, Pawelek says the work raises many questions: What causes a cancer cell to start producing these structures? What is the underlying relationship between expression of this trait and metastasis? And can the structures, particularly the sugars, be exploited for new directions in cancer therapy?

-- By Karen Peart

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Yale endowment reaches record high in last fiscal year

Pulitzer Prize-winning composer joins School of Music faculty

Experts on air pollution and energy systems join the F&ES faculty

Conference to explore the future of globalization

Team learns sugars produced by cancers may help disease spread

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Campus Notes