Collectin-11 promotes cancer cell proliferation and tumor growth
Jia-Xing Wang, Bo Cao, Ning Ma, Kun-Yi Wu, Wan-Bing Chen, Weiju Wu, Xia Dong, Cheng-Fei Liu, Ya-Feng Gao, Teng-Yue Diao, Xiao-Yun Min, Qing Yong, Zong-Fang Li, Wuding Zhou, Ke Li
Jia-Xing Wang, Bo Cao, Ning Ma, Kun-Yi Wu, Wan-Bing Chen, Weiju Wu, Xia Dong, Cheng-Fei Liu, Ya-Feng Gao, Teng-Yue Diao, Xiao-Yun Min, Qing Yong, Zong-Fang Li, Wuding Zhou, Ke Li
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Research Article Immunology Oncology

Collectin-11 promotes cancer cell proliferation and tumor growth

Abstract

Collectin-11 (CL-11) is a recently described soluble C-type lectin that has distinct roles in embryonic development, host defence, autoimmunity, and fibrosis. Here we report that CL-11 also plays an important role in cancer cell proliferation and tumor growth. Melanoma growth was found to be suppressed in Colec11–/– mice in a s.c. B16 melanoma model. Cellular and molecular analyses revealed that CL-11 is essential for melanoma cell proliferation, angiogenesis, establishment of more immunosuppressive tumor microenvironment, and the reprogramming of macrophages to M2 phenotype within melanomas. In vitro analysis revealed that CL-11 can activate tyrosine kinase receptors (EGFR, HER3) and ERK, JNK, and AKT signaling pathways and has a direct stimulatory effect on murine melanoma cell proliferation. Furthermore, blockade of CL-11 (treatment with L-fucose) inhibited melanoma growth in mice. Analysis of open data sets revealed that COLEC11 gene expression is upregulated in human melanomas and that high COLEC11 expression has a trend toward poor survival. CL-11 also had direct stimulatory effects on human tumor cell proliferation in melanoma and several other types of cancer cells in vitro. Overall, our findings provide the first evidence to our knowledge that CL-11 is a key tumor growth–promoting protein and a promising therapeutic target in tumor growth.

Authors

Jia-Xing Wang, Bo Cao, Ning Ma, Kun-Yi Wu, Wan-Bing Chen, Weiju Wu, Xia Dong, Cheng-Fei Liu, Ya-Feng Gao, Teng-Yue Diao, Xiao-Yun Min, Qing Yong, Zong-Fang Li, Wuding Zhou, Ke Li

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Figure 7

Treatment of mice with L-fucose inhibits melanoma growth.

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Treatment of mice with L-fucose inhibits melanoma growth. (A–G) WT mice ...
(A–G) WT mice that received treatment with saline or L-fucose (Fuc) daily by i.p. tumors were excised at d14 and used for analysis. (A) Representative images of tumors (n = 3 independent experiments). Scale bar: 5 μm. (B) Tumor weights. Data were analyzed by unpaired t test (n = 14 mice/group, pooled from 3 experiments). (C) Representative microscopy images of immunochemical staining for Ki67 (green)/CD45 (red)/DAPI (blue) in tumor core area. Scale bar: 25 μm. (D) Quantification of Ki67+/CD45– cells. Data are analyzed by unpaired t test (n = 12; 4 mice, 3 fields from each tumor section). (E) Representative microscopy images of immunochemical staining for CD31 (red)/DAPI (blue) in tumor core area. Scale bar: 50 μm. (F) Quantification of CD31. Data were analyzed by unpaired t test (n = 20; 4 mice, 5 fields from each tumor). (G) qPCR analysis of intratumor cytokines/chemokines. Data were analyzed by unpaired t test (n = 5 mice/group). (H and I) Tumors were excised at d14 from Colec11+/+ (WT) or Colec11–/– (KO) mice that received treatment with saline or Fuc daily. (H) Images of tumors. Scale bar: 5 μm. (I) Tumor weights. Data were analyzed by 1-way ANOVA with Tukey’s multiple-comparison test (n = 5 mice/group). H and I are representative of 2 independent experiments. (J and K) Representative microscopy images and flow cytometry histogram showing CL-11 (red) binding to B16 cells (DAPI) was blocked by Fuc (n = 3). Scale bar: 10 μm. (L) EdU proliferation assay in B16 melanoma cells following the treatment with rCL-11 or rCL-11 plus Fuc for 72 hours. Cell proliferation rate and total cell numbers were shown; each dot represents the average value of percentage of EdU+ cells, or cell numbers calculated from 5 image fields at 100× for each sample. Data were analyzed by paired t test (4 independent experiments). *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.