Regulation by proteins outside cancer cells points to potential new drug target

Vision is to reprogram cancer cells to state of permanent dormancy

2012-07-10

(Press-News.org) SAN ANTONIO (July 9, 2012) – Protein interactions outside breast cancer cells can send signals to the cancer cells to permanently stop proliferating, a new study showed in the School of Medicine at The University of Texas Health Science Center San Antonio.

"Because this protein cascade is outside the cells, it is likely amenable to therapeutic manipulation," said lead author Yuzuru Shiio, M.D., Ph.D., assistant professor of biochemistry at the university's Greehey Children's Cancer Research Institute. "I hope our study will ultimately lead to a therapeutic strategy to reprogram cancer cells to a state of permanent dormancy."

He cautions that the finding was observed in cell cultures and is still far from human cancer therapy. Dr. Shiio is also a member of the Cancer Therapy & Research Center (CTRC) at the UT Health Science Center, a National Cancer Institute Designated Cancer Center.

Senescence is poorly understood

Upon successful chemotherapy, cancer cells either die or permanently stop proliferation. The latter phenomenon is called senescence and is poorly understood, Dr. Shiio said.

Using cultured breast cancer cells as a model, the team found that upon chemotherapeutic drug treatment these cells released factors that stop proliferation. By analyzing which proteins are released under this stress, the team discovered that a protein called IGFBP3 (insulin-like growth factor binding protein 3) is a key player in cancer senescence. The team then studied other proteins that work together with IGFBP3 outside of the cancer cells.

Needle in a haystack

Using powerful, large-scale analysis called proteomics, the researchers literally picked out the increased abundance of this one protein, IGFBP3, among a thousand other proteins outside of the cells. It was like finding a proverbial needle in a haystack.

### National Institutes of Health grants AG029587, CA125020 and CA137568 to Dr. Shiio and an institutional grant, CA054174 (Cancer Therapy & Research Center at the UT Health Science Center San Antonio - Mass Spectrometry Shared Resource and Pathology Core Laboratory), supported this research in part.

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About the Cancer Therapy & Research Center at The University of Texas Health Science Center San Antonio The Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center at San Antonio is one of the elite academic cancer centers in the country to be named a National Cancer Institute (NCI) Designated Cancer Center, and is one of only four in Texas. A leader in developing new drugs to treat cancer, the CTRC Institute for Drug Development (IDD) conducts one of the largest oncology Phase I clinical drug programs in the world, and participates in development of cancer drugs approved by the U.S. Food & Drug Administration. For more information, visit www.ctrc.net.

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Regulation by proteins outside cancer cells points to potential new drug target

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