Title | Tumor Cell Associated Hyaluronan-CD44 Signaling Promotes Pro-Tumor Inflammation in Breast Cancer. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Witschen PM, Chaffee TS, Brady NJ, Huggins DN, Knutson TP, LaRue RS, Munro SA, Tiegs L, McCarthy JB, Nelson AC, Schwertfeger KL |
Journal | Cancers (Basel) |
Volume | 12 |
Issue | 5 |
Date Published | 2020 May 22 |
ISSN | 2072-6694 |
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 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. |
DOI | 10.3390/cancers12051325 |
Alternate Journal | Cancers (Basel) |
PubMed ID | 32455980 |
PubMed Central ID | PMC7281239 |
Grant List | 132574-CSDG-18-139-01-CSM / / American Cancer Society / P30 CA077598 / CA / NCI NIH HHS / United States T32 fellowship, OD010993 / NH / NIH HHS / United States R01CA235385 / NH / NIH HHS / United States R01 HD095858 / HD / NICHD NIH HHS / United States R01HD095858 / NH / NIH HHS / United States R01 CA215052 / CA / NCI NIH HHS / United States P30-CA077598 / / Masonic Cancer Center, University of Minnesota / |
Related Faculty:
Nicholas Brady, Ph.D.