Studys Focus Is On Prostate Cancer

    GRAND RAPIDS — Scientists at the Van Andel Research Institute launched a new study on prostate cancer a few months ago to try to gain a better understanding of what triggers the spread of the disease.

    The study, led by Scientific Investigator Cynthia Miranti, Ph.D., is focused on two prostate genes — CD82 and androgen receptor — and what happens to prostate cancer cells when the two genes cease functioning.

    Both genes normally function as metastasis suppressors, Miranti said.

    Previous research indicates CD82 controls cell movement. When CD82 is lost, prostate cells move more freely, Miranti explained. Loss of CD82 is known to occur in breast cancer tumors and other cancerous tumors, as well.

    The androgen receptor normally functions to help control prostate cell growth. Miranti and her team believe the loss of androgen receptor, too, might contribute to the spread of cancer to other sites in the body.

    “We basically have these two genes that get lost and somehow that unregulates cell motility and cell movement.

    “We want to know how their presence suppresses metastasis and what molecules they’re acting on to keep cells from metastasizing. When they’re lost, what other molecules get activated that shouldn’t be activated? Those then become the target for therapeutic intervention. Any way in which we can comprehend this process will help lead to a cure.”

    It’s not clear yet whether loss of the two genes absolutely guarantees the disease will spread or whether it’s a secondary step in the metastatic process, she said.

    “We’re trying to sequentially determine where in that pathway that their loss is important. It may occur early but doesn’t matter until later. A later step may have a function.

    “We’re using normal cells, which is a tool that a lot of other people don’t have, so we have a unique ability to ask what happens when the two genes are knocked out of the normal cells.”

    Previously, the study of prostate cancer was bogged down by scientists’ inability to culture normal human prostate cells, Miranti noted.

    Miranti and a postdoctoral fellow in her lab are collaborating on the study with a scientist from the Fred Hutchinson Cancer Research Center in Seattle who has successfully cultured normal prostate cells.

    Miranti also hooked up with Cold Spring Harbor Laboratories in New York for the project.

    “One of the molecules we think these metastatic genes are talking to is a molecule that this scientist at Cold Spring Harbor has knowledge about,” she explained.

    He has developed a technology for growing cells in three dimensions and is serving as a consultant to VARI on the techniques and protocols of 3-D culturing.

    “Normally, when we grow cells, we take them out of the host and put them in a Petri dish. Actually, that’s not the way cells grow in the body. We have a way of culturing cells in three dimensions that sort of mimics the way they are in the body and the way they see each other interact in the host. We think this is a more realistic presentation of cells.”

    Miranti noted there are other scientists investigating the loss of CD82, particularly in breast cancer, and she stays on top of their research, as well as shares her own. She brought fellow scientists up to date on her research at a conference in Rhode Island two weeks ago at the same time her postdoctoral fellow was spreading word about the research at a conference in Atlanta.

    “People were very excited about our recent data,” she said.

    The study is being funded by a three-year, $393,440 grant from the Department of Defense’s Prostate Cancer Research Program.

    Miranti earned her Ph.D. in biochemistry from Harvard and worked in the school’s department of cell biology until joining VARI in January 2000.           

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