Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2015 Apr 14;112(15):4725-30. doi: 10.1073/pnas.1424795112. Epub 2015 Mar 30.

CD14-expressing cancer cells establish the inflammatory and proliferative tumor microenvironment in bladder cancer.

Author information

1
Institute of Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305; Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University, Stanford, CA 94305; mingtc@stanford.edu jpvolkmer@stanford.edu irv@stanford.edu.
2
Institute of Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305; Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University, Stanford, CA 94305;
3
Institute of Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305; Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University, Stanford, CA 94305; Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093;
4
Institute of Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305; Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University, Stanford, CA 94305; Department of Obstetrics and Gynecology, University of Dusseldorf, 40225 Dusseldorf, Germany; and.
5
Division of Immunology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.

Abstract

Nonresolving chronic inflammation at the neoplastic site is consistently associated with promoting tumor progression and poor patient outcomes. However, many aspects behind the mechanisms that establish this tumor-promoting inflammatory microenvironment remain undefined. Using bladder cancer (BC) as a model, we found that CD14-high cancer cells express higher levels of numerous inflammation mediators and form larger tumors compared with CD14-low cells. CD14 antigen is a glycosyl-phosphatidylinositol (GPI)-linked glycoprotein and has been shown to be critically important in the signaling pathways of Toll-like receptor (TLR). CD14 expression in this BC subpopulation of cancer cells is required for increased cytokine production and increased tumor growth. Furthermore, tumors formed by CD14-high cells are more highly vascularized with higher myeloid cell infiltration. Inflammatory factors produced by CD14-high BC cells recruit and polarize monocytes and macrophages to acquire immune-suppressive characteristics. In contrast, CD14-low BC cells have a higher baseline cell division rate than CD14-high cells. Importantly, CD14-high cells produce factors that further increase the proliferation of CD14-low cells. Collectively, we demonstrate that CD14-high BC cells may orchestrate tumor-promoting inflammation and drive tumor cell proliferation to promote tumor growth.

KEYWORDS:

CD14; bladder cancer; inflammation; microenvironment

PMID:
25825750
PMCID:
PMC4403197
DOI:
10.1073/pnas.1424795112
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center