Yamaguchi-Tanaka Mio, Kurihara Yui, Takagi Kiyoshi, Sato Ai, Yasuda Iori, Yamazaki Yuto, Miyashita Minoru, Suzuki Takashi
Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi-Ken, 980-8575, Japan.
Department of Pathology, Tohoku University Hospital, 1-1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8574, Japan.
Breast Cancer. 2025 Sep 12. doi: 10.1007/s12282-025-01777-5.
C-type lectin-like domain family 2 (CLEC2D), a transmembrane protein, is a ligand for the inhibitory receptor CD161, which is expressed in several types of immune cells. CLEC2D expressed on cancer cells suppresses antitumor effect of these cells by interacting with CD161 in human malignancies. However, its clinical significance in breast cancer and its direct biological role in cancer cells remain largely unclear.
In this study, we immunolocalized CLEC2D in 174 breast cancer tissues and correlated its immunoreactivity with clinicopathological parameters and clinical outcomes. Additionally, we conducted in vitro assays to examine the effects of CLEC2D on the proliferation and migration of breast cancer cell lines.
CLEC2D immunoreactivity was predominantly detected in the cytoplasm of breast cancer cells and was associated with increased proliferation and invasion, as well as poor clinical outcomes especially in those who had received chemotherapy. In vitro experiments demonstrated that the knockdown of CLEC2D significantly suppressed the proliferation and migration of MCF-7, MDA-MB-231, T-47D breast cancer cells.
We therefore concluded that CLED2D directly promoted breast cancer cell proliferation and migration independently of immune cells and served as a poor prognostic factor in breast cancer.
C型凝集素样结构域家族2（CLEC2D）是一种跨膜蛋白，是抑制性受体CD161的配体，在多种免疫细胞中表达。癌细胞上表达的CLEC2D通过与人恶性肿瘤中的CD161相互作用来抑制这些细胞的抗肿瘤作用。然而，其在乳腺癌中的临床意义及其在癌细胞中的直接生物学作用仍不清楚。
在本研究中，我们对174例乳腺癌组织中的CLEC2D进行了免疫定位，并将其免疫反应性与临床病理参数及临床结局相关联。此外，我们进行了体外试验，以研究CLEC2D对乳腺癌细胞系增殖和迁移的影响。
CLEC2D免疫反应性主要在乳腺癌细胞的细胞质中检测到，并且与增殖增加、侵袭增加以及不良临床结局相关，尤其是在接受化疗的患者中。体外实验表明，敲低CLEC2D可显著抑制MCF-7、MDA-MB-231、T-47D乳腺癌细胞的增殖和迁移。
因此，我们得出结论，CLEC2D独立于免疫细胞直接促进乳腺癌细胞增殖和迁移，并作为乳腺癌的不良预后因素。
