Tumor Cell Associated Hyaluronan-CD44 Signaling Promotes Pro-Tumor Inflammation in Breast Cancer.

Autor: Witschen PM; Comparative and Molecular Biosciences Graduate Program, University of Minnesota, Minneapolis, MN 55455, USA., Chaffee TS; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA., Brady NJ; Microbiology, Immunology and Cancer Biology Graduate Program, University of Minnesota, Minneapolis, MN 55455, USA., Huggins DN; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA., Knutson TP; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.; University of Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN 55455, USA., LaRue RS; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.; University of Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN 55455, USA., Munro SA; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.; University of Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN 55455, USA., Tiegs L; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA., McCarthy JB; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA., Nelson AC; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA., Schwertfeger KL; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2020 May 22; Vol. 12 (5). Date of Electronic Publication: 2020 May 22.
DOI: 10.3390/cancers12051325
Abstrakt: Cancer has been conceptualized as a chronic wound with a predominance of tumor promoting inflammation. Given the accumulating evidence that the microenvironment supports tumor growth, we investigated hyaluronan (HA)-CD44 interactions within breast cancer cells, to determine whether this axis directly impacts the formation of an inflammatory microenvironment. Our results demonstrate that breast cancer cells synthesize and fragment HA and express CD44 on the cell surface. Using RNA sequencing approaches, we found that loss of CD44 in breast cancer cells altered the expression of cytokine-related genes. Specifically, we found that production of the chemokine CCL2 by breast cancer cells was significantly decreased after depletion of either CD44 or HA. In vivo, we found that CD44 deletion in breast cancer cells resulted in a delay in tumor formation and localized progression. This finding was accompanied by a decrease in infiltrating CD206+ macrophages, which are typically associated with tumor promoting functions. Importantly, our laboratory results were supported by human breast cancer patient data, where increased HAS2 expression was significantly associated with a tumor promoting inflammatory gene signature. Because high levels of HA deposition within many tumor types yields a poorer prognosis, our results emphasize that HA-CD44 interactions potentially have broad implications across multiple cancers.
Databáze: MEDLINE
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