Abstract
Abstract Carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 6 is a protein reported to be involved in tumor cell proliferation in breast cancer. The presence of intratumoral CEACAM8 positive neutrophils has been reported as an independent prognostic factor in both renal cell and hepatocellular cancer. In addition, CEACAM6 and 8 form a heterodimer; however, the possible interactions of these two proteins remain unclear in breast cancer. Therefore, in this study we first immunolocalized CEACAM6 and 8 in surgical pathology specimens of breast cancer. We examined 109 breast cancer and 20 metastatic breast cancer patients in this study. We then established MCF-7 cells (CEACAM6 positive) stably transfected with CEACAM8 and analyzed the interaction between CEACAM6 and CEACAM8 using proximity ligation assay (PLA) and further evaluated cell proliferation, invasion, and adhesion. Results of immunohistochemical analysis revealed that the number of CEACAM6 positive breast cancer cells was significantly higher in patients with low histological grade and stage also in CEACAM8 positive cells. The number of CEACAM6 and 8 double positive breast cancer cells was significantly higher in patients with low stage. In addition, CEACAM6 and 8 interaction was detected using the PLA through high expression of both in MCF-7 cells. Furthermore, their co-expression promoted cell adhesion of MCF-7 cells to the monolayer of endothelial cells but suppressed both cell invasion and proliferation. In metastatic breast cancer, CEACAM6 status was significantly higher in bone metastases than in lung metastases. To the best of our knowledge, this is the first study demonstrating the expressions of CEACAM6 and 8 in breast cancer. Results of our present study also indicated that both CEACAM6 and CEACAM8 could be involved in less aggressive subtypes of breast cancer possibly trough inhibition of vascular invasion and proliferation. In addition, results indicated that CEACAM6 was involved in breast cancer metastases to the bone but further studies are required to clarify the clinical significance of their interactions in breast cancer patients. Citation Format: Erina Iwabuchi, Yasuhiro Miki, Kiyoshi Takagi, Yoshiaki Onodera, Yukiko Shibahara, Takanori Ishida, Takashi Suzuki, Hironobu Sasano. The expression of carcinoembryonic antigen-related cell adhesion molecule 6 and 8 in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3066.
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