Journal
CLINICAL CANCER RESEARCH
Volume 14, Issue 19, Pages 5995-6004Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-08-0291
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Funding
- NCI NIH HHS [P30 CA036727, U01 CA111294-05, R01 CA057362, U01 CA111294, R01 CA057362-14, P30 CA036727-249008, T32 CA009476-19A1] Funding Source: Medline
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Purpose: We investigated the contribution of Sonic hedgehog (SHH) to pancreatic cancer progression. Experimental Design: We expressed SHH in a transformed primary ductal-derived epithelial cell line from the human pancreas, transformed hTert-HPNE (T-HPNE), and evaluated the effects on tumor growth. We also directly inhibited the activity of SHH in vivo by administering a blocking antibody to mice challenged orthotopically with the Capan-2 pancreatic cancer cell line, which is known to express SHH and form moderately differentiated tumors in nude mice. Results: Our data provide evidence that expression of SHH influences tumor growth by contributing to the formation of desmoplasia in pancreatic cancer. We further show that SHH affects the differentiation and motility of human pancreatic stellate cells and fibroblasts. Conclusions: These data suggest that SHH contributes to the formation of desmoplasia in pancreatic cancer, an important component of the tumor microenvironment.
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