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.
Yamaguchi et al. (2025) studied this question.