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

Co-expression of carcinoembryonic antigen-related cell adhesion molecule 6 and 8 inhibits proliferation and invasiveness of breast carcinoma cells
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DOI:
10.1007/s10585-019-09981-2
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发表时间:
2019-10-01
影响因子:
4
通讯作者:
Sasano, Hironobu
Sasano, Hironobu
中科院分区:
医学3区
文献类型:
--
作者:
Iwabuchi, Erina;Miki, Yasuhiro;Sasano, Hironobu

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癌胚抗原相关细胞粘附分子(CEACAM)6和CEACAM 8形成异二聚体并发挥其作用。因此,我们检查了CEACAM 6和CEACAM 8共表达在乳腺癌中的作用。我们首先研究了CEACAM 6/8的表达,免疫组化在109例乳腺癌患者。然后,我们建立了稳定转染CEACAM 8的MCF-7细胞,并研究了细胞增殖,侵袭和粘附。低组织病理学分级和低分期患者中CEACAM 6和CEACAM 8双阳性乳腺癌细胞数量显著增加。邻位连接测定(PLA)证实了MCF-7细胞中的高CEACAM 6/8表达。CEACAM 6/8表达促进MCF-7细胞与内皮细胞单层的粘附,但抑制其侵袭和增殖。此外,癌细胞中的CEACAM 6状态在骨中比在肺转移中显著更高。CEACAM 6/8表达与血管侵袭和细胞增殖的抑制有关。CEACAM 6的表达也被认为与乳腺癌的骨转移有关。这是第一项证明CEACAM 6/8异二聚体和CEACAM 6表达在乳腺癌患者中可能作用的研究。
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.