Fatty acid-binding protein E-FABP restricts tumor growth by promoting IFN-β responses in tumor-associated macrophages.
Fatty acid-binding proteins (FABP) are known central regulators of both metabolic and inflammatory pathways, but their role in tumor development remains largely unexplored. Here, we report that host expression of epidermal FABP (E-FABP) protects against mammary tumor growth. We find that E-FABP is highly expressed in macrophages, particularly in a specific subset, promoting their antitumor activity. In the tumor stroma, E-FABP-expressing tumor-associated macrophages (TAM) produce high levels of IFN-β through upregulation of lipid droplet formation in response to tumors. E-FABP-mediated IFN-β signaling can further enhance recruitment of tumoricidal effector cells, in particular natural killer cells, to the tumor stroma for antitumor activity. These findings identify E-FABP as a new protective factor to strengthen IFN-β responses against tumor growth.
Authors' Affiliations: The Hormel Institute, University of Minnesota, Austin; Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, Minnesota; and University of Texas Health Science Center, Tyler, Texas.
Yuwen
Y
Zhang
Authors' Affiliations: The Hormel Institute, University of Minnesota, Austin; Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, Minnesota; and University of Texas Health Science Center, Tyler, Texas.
Yanwen
Y
Sun
Authors' Affiliations: The Hormel Institute, University of Minnesota, Austin; Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, Minnesota; and University of Texas Health Science Center, Tyler, Texas.
Enyu
E
Rao
Authors' Affiliations: The Hormel Institute, University of Minnesota, Austin; Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, Minnesota; and University of Texas Health Science Center, Tyler, Texas.
Fei
F
Yan
Authors' Affiliations: The Hormel Institute, University of Minnesota, Austin; Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, Minnesota; and University of Texas Health Science Center, Tyler, Texas.
Qiang
Q
Li
Authors' Affiliations: The Hormel Institute, University of Minnesota, Austin; Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, Minnesota; and University of Texas Health Science Center, Tyler, Texas.
Ying
Y
Zhang
Authors' Affiliations: The Hormel Institute, University of Minnesota, Austin; Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, Minnesota; and University of Texas Health Science Center, Tyler, Texas.
Kevin A T
KA
Silverstein
Authors' Affiliations: The Hormel Institute, University of Minnesota, Austin; Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, Minnesota; and University of Texas Health Science Center, Tyler, Texas.
Shujun
S
Liu
Authors' Affiliations: The Hormel Institute, University of Minnesota, Austin; Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, Minnesota; and University of Texas Health Science Center, Tyler, Texas.
Edward
E
Sauter
Authors' Affiliations: The Hormel Institute, University of Minnesota, Austin; Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, Minnesota; and University of Texas Health Science Center, Tyler, Texas.
Margot P
MP
Cleary
Authors' Affiliations: The Hormel Institute, University of Minnesota, Austin; Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, Minnesota; and University of Texas Health Science Center, Tyler, Texas bli@hi.umn.edu.
Bing
B
Li
D000818:Animals; D004817:Epidermis / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000378:metabolism; D008055:Lipids / Q000235:genetics; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014407:Tumor Cells, Cultured
D050556:Fatty Acid-Binding Proteins; D008055:Lipids; D016899:Interferon-beta