PMID- 35239213 OWN - NLM STAT- MEDLINE DCOM- 20220422 LR - 20220422 IS - 1530-6860 (Electronic) IS - 0892-6638 (Linking) VI - 36 IP - 4 DP - 2022 Apr TI - Tumor microenvironment remodeling modulates macrophage phenotype in breast cancer lymphangiogenesis. PG - e22248 LID - 10.1096/fj.202101230R [doi] AB - Hyaluronan (HA) is dynamically remodeled in tumor microenvironment (TME) and is reported to be closely related to tumor lymphatic metastasis by inducing lymphangiogenesis. Macrophages are known to be involved in neo-lymphatic vessels formation. However, few studies have investigated the role of HA-mediated TME remodeling on macrophages-dependent lymphangiogenesis. We previously showed that HA could drive macrophages to acquire the M2 phenotype. In this study, we attempt to study the crosstalk between HA in TME and macrophages dependent lymphangiogenesis. First, we found that the abundant assembly of HA in breast cancer tissue was accompanied by increased infiltration of macrophages featured by expressing lymphatic endothelial markers. Then, to further identify the remodeling of HA in regulating macrophage phenotype, we used HA fragments which are usually enriched in TME for this purpose. Our results showed that the reconstructed HA could induce bone marrow-derived macrophages (BMDMs) to express markers of lymphatic endothelium and form tube-like structures, suggesting a novel function of HA from TME on macrophages-dependent lymphangiogenesis. Finally, we found that inhibition of the HA-TLR4 pathway could reduce the ability of BMDMs to exhibit lymphatic endothelial phenotype. Our results provide new insight into tumor microenvironment remodeling and macrophages in breast cancer lymphangiogenesis. CI - (c) 2022 Federation of American Societies for Experimental Biology. FAU - Du, Yan AU - Du Y AD - Department of Molecular Biology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P.R. China. AD - Department of Clinical Laboratory, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P.R. China. FAU - Cao, Manlin AU - Cao M AD - Department of Rehabilitation Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P.R. China. FAU - Liu, Yiwen AU - Liu Y AD - Department of Molecular Biology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P.R. China. FAU - He, Yiqing AU - He Y AD - Department of Molecular Biology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P.R. China. FAU - Yang, Cuixia AU - Yang C AD - Department of Molecular Biology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P.R. China. AD - Department of Clinical Laboratory, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P.R. China. FAU - Zhang, Guoliang AU - Zhang G AD - Department of Molecular Biology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P.R. China. FAU - Fan, Youben AU - Fan Y AD - Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P.R. China. FAU - Gao, Feng AU - Gao F AD - Department of Molecular Biology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P.R. China. AD - Department of Clinical Laboratory, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P.R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 RN - 9004-61-9 (Hyaluronic Acid) SB - IM MH - *Breast Neoplasms/metabolism MH - Female MH - Humans MH - Hyaluronic Acid/metabolism MH - Lymphangiogenesis MH - *Lymphatic Vessels/metabolism MH - Macrophages/metabolism MH - Phenotype MH - Tumor Microenvironment OTO - NOTNLM OT - LMW-HA OT - bone marrow-derived macrophages OT - hyaluronan remodeling OT - lymphangiogenesis OT - tumor microenvironment EDAT- 2022/03/04 06:00 MHDA- 2022/04/23 06:00 CRDT- 2022/03/03 12:20 PHST- 2022/02/11 00:00 [revised] PHST- 2021/08/02 00:00 [received] PHST- 2022/02/24 00:00 [accepted] PHST- 2022/03/03 12:20 [entrez] PHST- 2022/03/04 06:00 [pubmed] PHST- 2022/04/23 06:00 [medline] AID - 10.1096/fj.202101230R [doi] PST - ppublish SO - FASEB J. 2022 Apr;36(4):e22248. doi: 10.1096/fj.202101230R.