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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Nitric oxide regulates tumor cell cross-talk with stromal cells in the tumor microenvironment of the liver
American Journal of Pathology, Volume 173, No. 4, Year 2008
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Description
Tumor progression is regulated through paracrine interactions between tumor cells and stromal cells in the microenvironment, including endothelial cells and myofibroblasts. Nitric oxide (NO) is a key molecule in the regulation of tumor-microenvironment interactions, although its precise role is incompletely defined. By using complementary in vitro and in vivo approaches, we studied the effect of endothelial NO synthase (eNOS)-derived NO on liver tumor growth and metastasis in relation to adjacent stromal myofibroblasts and matrix because liver tumors maintain a rich, vascular stromal network enriched with phenotypically heterogeneous myofibroblasts. Mice with an eNOS deficiency developed liver tumors more frequently in response to carcinogens compared with control animals. In a surgical model of pancreatic cancer liver metastasis, eNOS overexpression in the tumor microenvironment attenuated both the number and size of tumor implants. NO promoted anoikis of tumor cells in vitro and limited their invasive capacity. Because tumor cell anoikis and invasion are both regulated by myofibroblast-derived matrix, we explored the effect of NO on tumor cell protease expression. Both microarray and Western blot analysis revealed eNOS-dependent down-regulation of the matrix protease cathepsin B within tumor cells, and silencing of cathepsin B attenuated tumor cell invasive capacity in a similar manner to that observed with eNOS overexpression. Thus, a NO gradient within the tumor microenvironment influences tumor progression through orchestrated molecular interactions between tumor cells and stroma. Copyright © American Society for Investigative Pathology.
Authors & Co-Authors
Decker, Ningling Kang
United States, Rochester
Mayo Clinic
United States, Rochester
Mayo Clinic in Rochester, Minnesota
Abdelmoneim, Soha Saoud
United States, Rochester
Mayo Clinic
Egypt, Asyut
Assiut University
Yaqoob, Usman
United States, Rochester
Mayo Clinic
Hendrickson, Helen
United States, Rochester
Mayo Clinic
Hormes, Joe
United States, Rochester
Mayo Clinic
Bentley, Mike
United States, Saint Paul
Minnesota State University
Pitot, Henry
United States, Madison
University of Wisconsin-madison
Urrutia, Raul
United States, Rochester
Mayo Clinic
Gores, Gregory J.
United States, Rochester
Mayo Clinic
Shah, Vijay H.
United States, Rochester
Mayo Clinic
United States, Rochester
Mayo Clinic in Rochester, Minnesota
Statistics
Citations: 42
Authors: 10
Affiliations: 5
Identifiers
Doi:
10.2353/ajpath.2008.080158
Research Areas
Cancer
Health System And Policy