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
. 2012 Dec;23(6):343-56.
doi: 10.1016/j.cytogfr.2012.06.006. Epub 2012 Jul 1.

Targeted destruction of the orchestration of the pancreatic stroma and tumor cells in pancreatic cancer cases: molecular basis for therapeutic implications

Xiangyu Kong  1 , Lei Li, Zhaoshen Li, Keping Xie
Affiliations
Review

Targeted destruction of the orchestration of the pancreatic stroma and tumor cells in pancreatic cancer cases: molecular basis for therapeutic implications

Xiangyu Kong et al. Cytokine Growth Factor Rev. 2012 Dec.

Abstract

Pancreatic cancer is one of the most lethal malignancies, with a prominent desmoplastic reaction as its defining hallmark. The past several decades have seen dramatic progress in understanding of pancreatic cancer pathogenesis, including identification of precursor lesions, sequential transformation from normal pancreatic tissue to invasive pancreatic cancer and corresponding signature genetic events, and the biological impact of these events on malignant behavior. However, the currently used therapeutic strategies for epithelial tumor cells, which have exhibited potent antitumor activity in cell culture and animal models, have failed to produce significant effects in the clinic. The desmoplastic stroma surrounding pancreatic cancer cells, which accounts for about 90% of a tumor's mass, clearly is not a passive scaffold for cancer cells but an active contributor to carcinogenesis. Improved understanding of the dynamic interaction between cancer cells and the stroma will be important to designing effective therapeutic strategies for pancreatic cancer. This review focuses on the origin of stromal molecular and cellular components in pancreatic tumors, their biological effects on pancreatic cancer cells, and the orchestration of these two components.

PubMed Disclaimer

Figures

Figure 1
Figure 1. H&E staining of human pancreatic ductal adenocarcinoma
Shown are a prominent desmoplastic reaction (white arrow head), neoplastic ductal cells (white arrow) tumor vasculature (black arrow head), and inflammatory cells (black arrow).
Figure 2
Figure 2. Signaling pathways bridging interactions between pancreatic cancer cells and stromal cells
1) Through different signaling pathways, including TGF-β, PDGF, IL-1, 6, 8, and etc., transformed tumor cells activate the quiescent stromal cells and initiate the extensive desmoplastic reaction; Microvesicles shed from tumor cells could also convey signals to target stromal cells through those bioactive molecules embedded within them. 2) Once activated, pancreatic stellate cells could perpetuate the desmoplastic reaction through a list of signaling pathways in an autocrine manner. Activated pancreatic stellate cells proliferate, contract, migrate, modulate extracellular matrix, and finally stimulate the growth and migration of tumor cells.
Figure 3
Figure 3. Schematic diagrams of four major sources of stromal cells
1) recruitment of pre-existing stromal cells; 2) transdifferentiation from mesenchymal stem cells; 3) Epithelial-to-mesenchymal transformation from epithelial tumor cells; and 4) transdifferentiation from cancer stem cells.
Figure 4
Figure 4. Candidate tumor stroma components for future targeted therapy
Included are abnormal blood vessels, deregulated signaling pathways, and various ECM compositions, e.g., SPARC and MMPs.
See this image and copyright information in PMC

References

    1. Huang C, Xie K. Crosstalk of Sp1 and Stat3 signaling in pancreatic cancer pathogenesis. Cytokine Growth Factor Rev. 2012;23:25–35. - PMC - PubMed
    1. Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011;61:212–236. - PubMed
    1. Xie K, Wei D, Huang S. Transcriptional anti-angiogenesis therapy of human pancreatic cancer. Cytokine Growth Factor Rev. 2006;17:147–156. - PubMed
    1. Haddad A, Kowdley GC, Pawlik TM, Cunningham SC. Hereditary pancreatic and hepatobiliary cancers. Int J Surg Oncol. 2011;2011:154673. - PMC - PubMed
    1. Brentnall TA. Management strategies for patients with hereditary pancreatic cancer. Curr Treat Options Oncol. 2005;6:437–445. - PubMed

Publication types