Sonic hedgehog promotes desmoplasia in pancreatic cancer.
OBJECTIVE
We investigated the contribution of Sonic hedgehog (SHH) to pancreatic cancer progression.


METHODS
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.
Bailey
Jennifer M
JM
Eppley Institute, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198, USA.
Swanson
Benjamin J
BJ
Hamada
Tomofumi
T
Eggers
John P
JP
Singh
Pankaj K
PK
Caffery
Thomas
T
Ouellette
Michel M
MM
Hollingsworth
Michael A
MA
D000818:Animals; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D005347:Fibroblasts / Q000378:metabolism; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D010179:Pancreas / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000628:therapy*
D053823:Hedgehog Proteins