期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 112, 期 15, 页码 4725-4730出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1424795112
关键词
bladder cancer; CD14; inflammation; microenvironment
资金
- National Cancer Institute of the National Institutes of Health [P01CA139490, R01CA86017]
- Siebel Foundation
- Virginia and D.K. Ludwig Fund for Cancer Research
- Smith Stanford Graduate Fellowship
- Dutch Cancer Society
- seed grant of the organization My Blue Dots
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 formlarger tumors comparedwith 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 immunesuppressive 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 cellsmay orchestrate tumor-promoting inflammation and drive tumor cell proliferation to promote tumor growth.
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