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Published on: November 19, 2019
Sonic hedgehog promotes desmoplasia in pancreatic cancer
Jennifer M Bailey1, Benjamin J Swanson, Tomofumi Hamada
1Eppley Institute, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198, USA.
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.
Insights
Sonic hedgehog (SHH) signaling promotes pancreatic cancer growth by driving desmoplasia. SHH also impacts the differentiation and motility of pancreatic stellate cells and fibroblasts, key components of the tumor microenvironment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Pancreatic cancer is a deadly disease with a complex tumor microenvironment.
- Desmoplasia, a hallmark of pancreatic cancer, significantly influences tumor progression and therapeutic response.
Purpose of the Study:
- To investigate the role of Sonic hedgehog (SHH) signaling in pancreatic cancer progression.
- To determine how SHH influences tumor growth and the tumor microenvironment.
Main Methods:
- Expressed SHH in human pancreatic ductal epithelial cells (T-HPNE) to assess tumor growth.
- Administered a blocking antibody against SHH in mice orthotopically implanted with SHH-expressing Capan-2 pancreatic cancer cells.
Main Results:
- SHH expression was found to contribute to desmoplasia formation in pancreatic cancer.
- SHH signaling affects the differentiation and motility of human pancreatic stellate cells and fibroblasts.
Conclusions:
- SHH plays a significant role in promoting desmoplasia within the pancreatic cancer tumor microenvironment.
- Targeting SHH may offer a therapeutic strategy to modulate the tumor microenvironment and inhibit pancreatic cancer progression.
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