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. 2019 May 27;121(1):22–33. doi: 10.1038/s41416-019-0482-x

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 6 — HGF chemoattracts the migration of tumour-associated M2 macrophages accumulated in sorafenib-resistant tumours. a HGF chemoattracts the migration of M2 macrophage but not M1 macrophage as determined by transwell migration assays. b Experimental procedures for development of sorafenib-resistant xenograft models by passage of HCC cells in nude mice, inducible treatment of mice with sorafenib, and implantation of mouse-passaged tumour cells in mice again. c Daily sorafenib treatment inhibited hepatoma growth in immunocompromised mice for the first round of xenograft. N = 5–6, Mean ± SEM, *P < 0.05. Tumour growth in individual mouse was shown in Supplementary Fig. 2a. d Daily sorafenib treatment of the mice greatly inhibited the tumour growth on sorafenib-sensitive (SS) tumour models (SS-Sor versus SS-DMSO, P < 0.01) but marginally affected the tumour growth on sorafenib-resistant (SR) tumour models (SR-Sor versus SR-DMSO, P > 0.05). N = 5–7, mean ± SEM, **P < 0.01, NS, no significance. e Flow cytometry assays showing SR-DMSO tumour contains more F4/80⁺ and CD206⁺ double positive M2 macrophages than that of SR-Sor tumour [SR-DMSO (N = 3) versus SR-Sor (N = 4), P < 0.05] or SS-DMSO tumour [SR-DMSO (N = 3) versus SS-DMSO (N = 3), P < 0.05)]. Mean ± SEM, *P < 0.05, NS, no significance