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Metastatic profiling of HER2-positive breast cancer cell lines in xenograft models

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Abstract

Most studies on breast cancer metastasis have been performed using triple-negative breast cancer cells; thus, subtype-dependent metastatic ability of breast cancer is poorly understood. In this research, we performed intravenous injection (IVI) and intra-caudal arterial injections using nine human epidermal growth factor receptor-2 (HER2)-positive breast cancer cell lines for evaluating their metastatic abilities. Our results showed that MDA-MB-453, UACC-893, and HCC-202 had strong bone metastatic abilities, whereas HCC-2218 and HCC-1419 did not show bone metastasis. HER2-positive cell lines could hardly metastasize to the lung through IVI. From the genomic analysis, gene signatures were extracted according to the breast cancer subtypes and their metastatic preferences. The UACC-893 cell line was identified as a useful model for the metastasis study of HER2-positive breast cancer. Combined with our previous result on brain metastasis ability, we provide a characteristic metastasis profile of HER2-positive breast cancer cell lines in this study.

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Data availability

The data of presented study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank Ms Yuka Kuroiwa and laboratory members for the meaningful comments and discussion.

Funding

This study was supported by JSPS KAKENHI (Grant No. 18K16269: Grant-in-Aid for Early-Career Scientist to JN; Grant No. 20J01794, Grant-in-Aid for JSPS fellows to JN; Grant No. 20J23297, Grant-in-Aid for JSPS fellows to YH) and partially supported by the grants for translational research programs from Fukushima Prefecture (SW and KS).

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Authors and Affiliations

  1. Department of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, TWIns, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo, 162-8480, Japan

    Yuxuan Han, Kazushi Azuma, Kentaro Semba & Jun Nakayama

  2. Translational Research Center, Fukushima Medical University, Fukushima, Japan

    Shinya Watanabe & Kentaro Semba

  3. Laboratory of Integrative Oncology, National Cancer Center Research Institute, Tokyo, Japan

    Jun Nakayama

Authors
  1. Yuxuan Han
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  2. Kazushi Azuma
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  3. Shinya Watanabe
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  4. Kentaro Semba
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  5. Jun Nakayama
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Contributions

YH and KA performed the in vivo experiments. YH preformed the bioinformatics analyses. SW and KS interpreted the data. YH, KA, and JN wrote the manuscript. JN conceived and designed the study. All the authors reviewed and edited the manuscript.

Corresponding author

Correspondence to Jun Nakayama.

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Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

The animal experiments were conducted under the approval of the ethics committee of Waseda University (2020-A067, 2021-A074).

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Supplementary Information

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10585_2022_10150_MOESM1_ESM.tif

Supplementary Fig. S1 Evaluation of bone metastasis potential of HER2-positive cell lines. The bone metastatic tumors of all transplanted mice (n = 4) at week 8 were observed and summarized. (a) High bone metastatic potential group. (b) Non-high bone metastatic potential group. One of the mice transplanted with BT-474 died during the observation. The mouse indicated with a yellow star exhibited metastatic tumors other than bone tumors. (c) Average tumor size ± standard error of the mean at week 8 for each cell line (TIF 111426 kb)

10585_2022_10150_MOESM2_ESM.tif

Supplementary Fig. S2 Transplantation of the HER2-positive cell lines via IVI. UACC-893, HCC-202, MDA-MB-453, ZR-75–1, HCC-1419, HCC-2218, BT-474, MDA-MB-361, and UACC-812 cells were intravenously injected in the NOD-SCID mice (MDA-MB-453, n = 9; UACC-893, n = 7; HCC-202, n = 5; MDA-MB-361, n = 3; others, n = 4). (a) Lung metastasis was quantified by measuring bioluminescence every week. Left: Bioluminescence on week 1. Right: Bioluminescence on week 8. (b) The lungs were removed from each mouse after the 8-week measurement, and luminescence from the lung was detected using ex vivo BLI (TIF 93701 kb)

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Han, Y., Azuma, K., Watanabe, S. et al. Metastatic profiling of HER2-positive breast cancer cell lines in xenograft models. Clin Exp Metastasis 39, 467–477 (2022). https://doi.org/10.1007/s10585-022-10150-1

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  • DOI: https://doi.org/10.1007/s10585-022-10150-1

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