Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2013;18(1-2):135-51.
doi: 10.1615/critrevoncog.v18.i1-2.80.

Tumor-stromal interactions in pancreatic cancer

Clifford Whatcott  1 , Haiyong Han, Richard G Posner, Daniel D Von Hoff
Affiliations
Review

Tumor-stromal interactions in pancreatic cancer

Clifford Whatcott et al. Crit Rev Oncog. 2013.

Abstract

The tumor associated stroma has been described in recent years as being complicit in tumor growth in pancreatic cancer. The stroma hosts a variety of components of both cellular and molecular makeup. In normal tissues, the stroma provides nutrients and regulatory signals for proper cellular polarity and function. However, following oncogenic transformation, the stromal compartment is conscripted to provide stimulatory signals and protection to tumor cells. It is these tumor-stromal interactions that are currently of great therapeutic interest. Several key reports have suggested that therapeutic targeting of the tumor-stromal interactions in pancreatic cancer has the potential to offer survival benefit. In this review, we will discuss the tumor-stromal interactions that contribute to tumor growth and progression, and ways in which we might counter these interactions.

PubMed Disclaimer

Figures

FIGURE 1
FIGURE 1
Tumor-stroma interactions in pancreatic cancer. PDAC is characterized by the development of the desmoplastic reaction, which features growth of the CAF cell compartment, and deposition of ECM components. Reciprocal growth factor signaling results in increased expression of growth factors such as IGF, EGF, and TGFβ. In addition, interactions with the immune cell and endothelial cell compartment contribute to tumorigenesis through the release of ROS and additional growth factors. Interactions with each of these compartments contribute to the enhanced growth of tumors in PDAC. Each quadrant heading corresponds to a section title and topic to be covered in the following review.
FIGURE 2
FIGURE 2
Histochemical analysis of human pancreatic tissue samples. Both normal and tumor pancreatic tissues were subjected to hematoxylin/eosin (H&E) and pentachrome (Russell-Movat’s) staining analysis. H&E analysis reveals increased proliferation of the pancreatic stellate cell population in the tumor tissues relative to normal tissues. Pentachrome analysis also demonstrates increased collagen expression in the stromal compartment in tumor tissue relative to normal tissue. Pentachrome staining: Green/blue=mucins, Yellow=collagen, Red=muscle/fibrinoid. Scale bar=100 μm
FIGURE 3
FIGURE 3
Primary signaling pathways mediated by the integrin receptors and CD44. Integrin signaling functions directly via FAK and either GRB2/SOS/Ras, or via the PI3K-AKT signaling axis. The integrin family of receptors promotes cell survival, proliferation, migration, and invasion. CD44 also mediates PI3K-AKT signaling via RhoA/ROCK, which promotes cell survival, proliferation, and migration.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Paget S. The distribution of secondary growths in cancer of the breast. The Lancet. 1889;133:571–73. - PubMed
    1. Siegel R, Naishadham D, Jemal A. Cancer statistics. CA Cancer J Clin. 2012;62:10–29. - PubMed
    1. Mahadevan D, Von Hoff DD. Tumor-stroma interactions in pancreatic ductal adenocarcinoma. Mol Cancer Ther. 2007;6:1,186–97. - PubMed
    1. Yen TW, Aardal NP, Bronner MP, Thorning DR, Savard CE, Lee SP, Bell RH., Jr Myofibroblasts are responsible for the desmoplastic reaction surrounding human pancreatic carcinomas. Surgery. 2002;131:129–34. - PubMed
    1. Magzoub M, Jin S, Verkman AS. Enhanced macromolecule diffusion deep in tumors after enzymatic digestion of extracellular matrix collagen and its associated proteoglycan decorin. FASEB J. 2008;22:276–84. - PubMed

Publication types

MeSH terms