These studies represent a potential mechanism by which CXL12 may slow cancer spreading. Controlling this process could lead to new biological therapies for colorectal cancers.
"Colorectal cancer ranks third in cancer-related deaths in the United States in 2008," says principal investigator Michael Dwinell, Ph.D., professor of microbiology and molecular genetics. "Finding therapies to prevent its spread to secondary organs would increase patient prognosis considerably." Luke Drury, a graduate student in the interdisciplinary program for biomedical research at the Medical College, was his research associate. Their abstract will be presented at the American Association for Cancer Research meeting in Denver, April 21.
Normal intestinal cells stick to underlying proteins, which provide survival signals to maintain cell health. If they become unstuck, the floating cells undergo a programmed cell death. In cancer, cells have acquired genetic changes that allow them to survive during loss of attachment. Previously, the researchers found that colorectal cancer cells lacked CXCL12 expression. In these studies, they re-introduced CXCL12 expression in colorectal cancer cells which prevented their ability to adhere to underlying proteins. Plus, the floating cells underwent programmed cell death.
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This mouse model of WHS provides a valuable new tool for researchers studying this developmental disorder. It provides a new avenue for molecular research through study of Fgrf1 function, but also allows scientists to understand how structural defects might contribute to WHS symptoms, as is the case in the heart defects and swallowing difficulties.
The report, "Multiple congenital malformations of Wolf-Hirschhorn syndrome are recapitulated in Fgfrl1 null mice" was Catarina Catela, Daniel Bilbao-Cortes, Esfir Slonimsky, Paschalis Kratsios, Nadia Rosenthal and Pascal te Welscher of the European Molecular Biology Laboratory in Monterotondo, Italy. The report is published in the May/June issue of Disease Models & Mechanisms (DMM), a research journal published by The Company of Biologists, a non-profit based in Cambridge, UK.
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