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Co-expression of carcinoembryonic antigen-related cell adhesion molecule 6 and 8 inhibits proliferation and invasiveness of breast carcinoma cells

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Abstract

The carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 6 and CEACAM8 form heterodimers and exert their effects. Therefore, we examined the effects of CEACAM6 and CEACAM8 co-expression in breast cancer. We first studied CEACAM6/8 expression using immunohistochemistry in 109 patients with breast cancer. We then established MCF-7 cells that were stably transfected with CEACAM8 and studied cell proliferation, invasion and adhesion. The number of CEACAM6 and CEACAM8 double-positive breast carcinoma cells significantly increased in patients with low histopathological grade and stage. Proximity ligation assay (PLA) confirmed high CEACAM6/8 expression in MCF-7 cells. CEACAM6/8 expression promoted the adhesion of MCF-7 cells to endothelial cell monolayers but inhibited their invasion and proliferation. Furthermore, CEACAM6 status in carcinoma cells was significantly higher in bone than in lung metastases. CEACAM6/8 expression is associated with the inhibition of vascular invasion and cell proliferation. CEACAM6 expression was also considered to be involved in bone metastases of breast cancer. This is the first study to demonstrate the possible role of CEACAM6/8 heterodimer and CEACAM6 expression in breast cancer patients.

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Acknowledgements

We thank Mr. Katsuhiko Ono, Ms. Kazue Ise, and Ms. Akiko Morohashi for their supports. EI is supported by Research Fellowship for Young Scientists from Japan Society for the Promotion of Science (JSPS).

Funding

EI was supported by Research Fellowship for Young Scientists from Japan Society for the Promotion of Science (JSPS) with Grant No. 18J10855.

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Authors and Affiliations

  1. Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan

    Erina Iwabuchi, Yoshiaki Onodera, Yukiko Shibahara & Hironobu Sasano

  2. Japan Society for the Promotion of Science, Tokyo, Japan

    Erina Iwabuchi

  3. Department of Disaster Obstetrics and Gynecology, International Research Institute of Disaster Science (IRIDes), Tohoku University, Sendai, Japan

    Yasuhiro Miki

  4. Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada

    Yukiko Shibahara

  5. Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Japan

    Kiyoshi Takagi & Takashi Suzuki

  6. Department of Breast and Endocrine Surgical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan

    Takanori Ishida

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  1. Erina Iwabuchi
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Correspondence to Hironobu Sasano.

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The study was performed in accordance with the Declaration of Helsinki. Approval for the study was obtained from the ethics committee at Tohoku University.

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Iwabuchi, E., Miki, Y., Onodera, Y. et al. Co-expression of carcinoembryonic antigen-related cell adhesion molecule 6 and 8 inhibits proliferation and invasiveness of breast carcinoma cells. Clin Exp Metastasis 36, 423–432 (2019). https://doi.org/10.1007/s10585-019-09981-2

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