31 Mar Medical College of Wisconsin ties breast cancer to inflammation
MILWAUKEE – Researchers at the Medical College of Wisconsin, led by Ashwani Khanna, an associate professor of medicine in nephrology, are studying the role inflammation may play in initiating breast cancer, specifically by looking at certain proteins known to play a role in inflammation, and their presence in breast cancer. In two separate studies they found a marked increase in some of these proteins in tissue from breast cancer patients as compared to tissue from a control group.
“Our results identify the role inflammation plays in breast cancer initiation and development,” Khanna said.. “In addition, monitoring these markers can prove useful in diagnosis of doubtful cases.”
Khanna presented his findings at the annual meeting of the American Association for Cancer Research March 30 in Orlando. “We know that inflammation can be triggered in response to a number of factors including environmental, hormonal, genetic or infections,” Khanna said. “However, research shows that when the condition becomes chronic, it can lead to a great many diseases, including cancers.”
In the first study, Khanna and his colleagues looked at 14 samples of normal breast tissue and 14 tissue samples from patients with breast cancer. The research team included Matthew Plummer, lab technician; Chitra Sadasiwan, M. D., clinician in training; Anna Purdy, R.N., nurse practioner in surgery; and Alonzo Walker, M. D., professor of surgery. They examined the expression of different genes in tissues and lymphocytes – a form of white blood cells in lymph glands – from the breast cancer patients and controls. Specifically, they examined the expression of a protein known to play a role in cellular differentiation and proliferation, called peroxisome proliferator-activated receptor; and other proteins released during inflammation, known as chemokines and integrins. They also examined the role of caspases enzymes in programmed cell death.
The group found an increased expression of peroxisome, chemokines and integrins in the cancerous tissue. There were also significant increases in several types of caspases in the lymphocytes from breast cancer patients.
“These results demonstrate that differential expression of these proteins can provide valuable information in differentiating malignant from normal tissue,” Khanna said.
The second study looked at the expression of two breast specific markers – mmaglobin B and Skp2 mRNA as a means to detect tumor. Mammaglobin B, which is present in normal breast tissue, is activated after injury to the breast and therefore can help to find malignancy. Abnormal cells proliferate in cancer because the normal cell cycle regulators are disrupted. Skp2 is one of the factors responsible for that.
Though explored in breast cancer cell lines, their role in breast cancer patients has not been studied in detail. Khanna believes this will be only the second study to explore mammaglobin B and the first study examining Skp2 mRNA expression in breast cancer patients. The Medical College researchers hypothesized that the expression of these molecules would be higher in cancer patients. They again looked at breast tissue from 14 cancer patients and from 14 women without breast cancer. They also examined lymphocytes from the same patients and compared them to lymphocytes from six of the non-cancer group. The group found a statistically significant increase in the two proteins in the breast cancer tissue and in lymphocyte tissue.
“These results demonstrate that both these markers can strongly identify malignant cells and can assist in better diagnosis of breast cancer patients, especially those at higher risk,” Khanna said.
The tissue samples were obtained from Froedtert Hospital, the Medical College Breast Care Clinic and from the Cooperative Human Tissue Network, which is supported by the National Cancer Institute to provide biomedical researchers access to human tissues.
“About 40,000 women died from breast cancer last year. The only way we are going to reduce this number substantially is to gain a better understanding of the disease and its causes. The findings reported by Dr. Khanna and his team add significantly to that understanding,” said William Hendee, senior associate dean and vice president of the Medical College.