title: A novel role of breast cancer-derived hyaluronan on inducement of M2-like tumor-associated macrophages formation.
abstract: Microenvironmental signals determine the differentiation types and distinct functions of macrophages. Tumor-associated macrophages (TAM) constitute major infiltrates around solid tumor cells and accelerate tumor progression due to their immunosuppressive functions. However, the mechanisms through which tumor microenvironment modulates macrophages transition are not completely elucidated. Hyaluronan (HA), a prominent component in tumor microenvironment, is a notable immunoregulator and its high level is often related to poor prognosis. Herein, we found that the number of M2 macrophages was highly correlated with HA expression in tumor tissues from breast cancer patients. Experimental data showed that breast cancer-derived HA stimulated M2-like TAM formation in a mouse model and had multiple effects on macrophages transformation in vitro, including upregulating CD204, CD206, IL-10 and TGF-β, activating STAT3 signal, and suppressing killing capacity. These data indicate that HA derived from breast cancer activates macrophages in an alternative manner. Further mechanism study revealed that HA-CD44-ERK1/2-STAT3 pathway served as an important regulator in M2-like TAM formation. Therefore, targeting TAM by abrogating HA-CD44 interaction may be a potential strategy for breast cancer immunotherapy.
authors.affiliation: Department of Molecular Biology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai, P. R. China.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of clinical Laboratory, Shanghai Oncology Hospital, Shanghai Fudan University School of Medicine , Shanghai, P. R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Molecular Biology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai, P. R. China.
authors.forename: Cuixia
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Molecular Biology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai, P. R. China.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Molecular Biology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai, P. R. China.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Molecular Biology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Molecular Biology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai, P. R. China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Molecular Biology and Clinical Laboratory, Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai, P. R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
keywords: Breast cancer; CD44; ERK1/2; STAT3; hyaluronan; tumor-associated macrophages