Tags

Type your tag names separated by a space and hit enter

Tumor Cell Associated Hyaluronan-CD44 Signaling Promotes Pro-Tumor Inflammation in Breast Cancer.
Cancers (Basel). 2020 May 22; 12(5)C

Abstract

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.

Authors+Show Affiliations

Comparative and Molecular Biosciences Graduate Program, University of Minnesota, Minneapolis, MN 55455, USA.Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.Microbiology, Immunology and Cancer Biology Graduate Program, University of Minnesota, Minneapolis, MN 55455, USA.Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.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.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.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.Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA. Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA. Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.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.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32455980

Citation

Witschen, Patrice M., et al. "Tumor Cell Associated Hyaluronan-CD44 Signaling Promotes Pro-Tumor Inflammation in Breast Cancer." Cancers, vol. 12, no. 5, 2020.
Witschen PM, Chaffee TS, Brady NJ, et al. Tumor Cell Associated Hyaluronan-CD44 Signaling Promotes Pro-Tumor Inflammation in Breast Cancer. Cancers (Basel). 2020;12(5).
Witschen, P. M., Chaffee, T. S., Brady, N. J., Huggins, D. N., Knutson, T. P., LaRue, R. S., Munro, S. A., Tiegs, L., McCarthy, J. B., Nelson, A. C., & Schwertfeger, K. L. (2020). Tumor Cell Associated Hyaluronan-CD44 Signaling Promotes Pro-Tumor Inflammation in Breast Cancer. Cancers, 12(5). https://doi.org/10.3390/cancers12051325
Witschen PM, et al. Tumor Cell Associated Hyaluronan-CD44 Signaling Promotes Pro-Tumor Inflammation in Breast Cancer. Cancers (Basel). 2020 May 22;12(5) PubMed PMID: 32455980.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tumor Cell Associated Hyaluronan-CD44 Signaling Promotes Pro-Tumor Inflammation in Breast Cancer. AU - Witschen,Patrice M, AU - Chaffee,Thomas S, AU - Brady,Nicholas J, AU - Huggins,Danielle N, AU - Knutson,Todd P, AU - LaRue,Rebecca S, AU - Munro,Sarah A, AU - Tiegs,Lyubov, AU - McCarthy,James B, AU - Nelson,Andrew C, AU - Schwertfeger,Kathryn L, Y1 - 2020/05/22/ PY - 2020/04/13/received PY - 2020/05/15/revised PY - 2020/05/19/accepted PY - 2020/5/28/entrez PY - 2020/5/28/pubmed PY - 2020/5/28/medline KW - CD44 KW - breast cancer KW - hyaluronan KW - inflammation KW - tumor microenvironment JF - Cancers JO - Cancers (Basel) VL - 12 IS - 5 N2 - 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. SN - 2072-6694 UR - https://www.unboundmedicine.com/medline/citation/32455980/Tumor_Cell_Associated_Hyaluronan-CD44_Signaling_Promotes_Pro-Tumor_Inflammation_in_Breast_Cancer L2 - https://www.mdpi.com/resolver?pii=cancers12051325 DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.