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. 2022 Mar 3;41:81. doi: 10.1186/s13046-022-02300-w

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© The Author(s) 2022

Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 6 — CCL5 promotes collagen synthesis via fibroblasts, contributing to tumor progression. a The differentially expressed genes in the transcriptome sequencing were analyzed by GO functional enrichment analysis. b Immunoblots for COL1 and COL3 protein expression in CCD-18Co and human primary normal colorectal fibroblast (NF4) before and after 40 ng/ml CCL5 stimulation for 24 h. c IHC scores of CCL5 in human adjacent normal tissues and CRC tumor tissues. Data, adjacent, n = 162; tumor, n = 195. (d) Spearman’s correlation analysis of low and high expression of CCL5 in human CRC patients with the different tumor budding categories. Spearman r = 0.583. Data, n = 195. e Scores of Sirius Red staining in human adjacent normal tissues and CRC tumor tissues. Data, adjacent, n = 82; tumor, n = 88. f Spearman’s correlation analysis of low and high level of Sirius Red staining in human CRC patients with the different tumor budding categories. Spearman r = 0.297. Data, n = 88. g Representative CCL5 IHC staining and Sirius Red staining images of human CRC tissue at the invasive front without (the left panel) or with (the right panel) tumor budding. The red triangles indicate the tumor buds. Scale bar, 50 μm. h Spearman’s correlation analysis between the level of CCL5 expression and Sirius Red staining in human CRC tissues. Spearman r = 0.317. Data, n = 88. i Representative Sirius Red staining images of normal mouse caecum and tumor tissue in the mouse caecum. Data, normal, n = 5; tumor, n = 5. Scale bar, 50 μm. j Kaplan–Meier survival analysis of CRC patients with low and high expression of COL1 mRNA or COL3 mRNA in the human CRC microarray profile GSE39582. Data, n = 566. k Schematic diagram of the contribution of tumor bud-derived CCL5 to the TME at the invasive front. ns, no significance; *, P < 0.05; **, P < 0.01; ***, P < 0.001 by Mann–Whitney U test (c, e), Spearman’s correlation test (d, f, h), log-rank test (j)