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Study suggests ovarian cancer cells can alter surroundings to promote chemotherapy resistance

Compelling new scientific evidence suggests cancer cells can trigger changes in their immediate surroundings that promote self-preservation. Collagen VI, a protein produced by ovarian cancer cells, appears to help these cells alter their microenvironment so they are more resistant to chemotherapeutic drugs commonly used to treat the disease, according to investigators at the National Institute on Aging (NIA) Intramural Research Program and colleagues at other research centers.

"It has been known for some time that the microenvironment of cancer cells can affect the response of these cells to chemotherapy. But our data show that cancer cells can remodel their surroundings to make themselves more resistant to chemotherapy. This is quite an intriguing concept," says Patrice Morin, Ph.D., an investigator specializing in cancer molecular genetics in the NIA's Laboratory of Cellular and Molecular Biology. The findings* are reported in the April 2003 issue of Cancer Cell.

Blocking the production or the effects of collagen VI in ovarian cancer cells could increase the effectiveness of chemotherapy treatments and improve survival rates for this cancer, which occurs most frequently in women older than 50 who have gone through menopause, Dr. Morin says.

"Drug resistance is a major problem in cancer treatment in general, and in ovarian cancer in particular," he says. "We were interested in finding out the mechanisms of resistance. Just how is it that cancer cells become resistant to chemotherapy?"

To find out, Dr. Morin and his colleagues used serial analysis gene expression (SAGE) technology to examine more than 15,000 common genes in two ovarian cancer cell lines with differing degrees of resistance to chemotherapy. SAGE is a new tool to evaluate the genes expressed in cells of interest. After analyzing their findings, the investigator found only 16 genes that were differentially up or down regulated in the cell line that was most resistant
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Contact: Doug Dollemore
dollemod@nia.nih.gov
301-496-1752
NIH/National Institute on Aging
21-Apr-2003


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