The researchers checked for Hedgehog activation in cell lines and fresh samples of digestive tract tumors because the gut comes from the same part of the embryo -- the endoderm -- as the lung, says Anirban Maitra, MBBS, assistant professor of pathology. Earlier this year, a team from Hopkins linked Hedgehog activation to small cell lung cancer, providing reason to anticipate Hedgehog's involvement in a variety of other cancers, notes Berman.
"Because of Hedgehog's important roles in these tissues during development, we hypothesized that 'reactivation' of the pathway occurs in adult life during cancer development in these organs," adds Maitra, whose procedure for obtaining fresh samples from surgically removed tumors provided the opportunity to analyze cancers unaltered by years of laboratory growth. "Our studies prove this hypothesis to be true."
The pathway's link to another batch of cancers support the idea that cancer may arise -- in part -- from abnormal growth of stem cells inside mature organs.
The scientists speculate that primitive cells in the lining of the digestive tract may turn on the normal Hedgehog pathway to repair tissue damaged by long-term exposure to an environmental toxin or irritant, such as excess stomach acid chronically rising into the esophagus.
If the damaging environmental irritant is also carcinogenic, such as tobacco smoke, the chances go up that these long-lived primitive cells eventually may collect the right genetic mutations to trigger cancer development, suggests Beachy.
Authors on the study linking Hedgehog to digestive tract tumors are Berman, Maitra, Beachy, Sunil Karhadkar, Rocio Montes de Oca, Meg Gerstenblith, Antony Parker and James Eshleman of the Johns Hopkins School of Medicine; Kimberly Briggs and Neil Watkins of the Johns Hopkins Kimmel Cancer Center; and Yutaka Shimada of Kyoto University, Japan. The pr
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
22-Oct-2003