Breast cancer cells expressing cancer-associated sialyl-Tn antigen have less capacity to develop osteolytic lesions in a mouse model of skeletal colonization

• DOI: 10.1007/s10585-019-09999-6
• Publication Date: 2019-10-08T08:03:11Z
• Authors: Ryo Fujita; Hiroki Hamano; Yusuke Kameda; Ryuta Arai; Tomohiro Shimizu; Masahiro Ota; Dai Sato; Hideyuki Kobayashi; Norimasa Iwasaki; Masahiko Takahata
• Keywords: 0301 basic medicine; Mice, Inbred BALB C; Integrin beta1; Mice, Nude; Apoptosis; Bone Neoplasms; Breast Neoplasms; Xenograft Model Antitumor Assays; Sialyltransferases; Fibronectins; 3. Good health; Mice; 03 medical and health sciences; Cell Movement; Osteogenesis; Cell Adhesion; Tumor Cells, Cultured; Animals; Humans; Antigens, Tumor-Associated, Carbohydrate; Female; Cell Proliferation

Breast cancer is one of the most prevalent malignancies in women, and approximately 75-80% of patients with advanced breast cancer develop bone metastasis. Expression of the cancer-associated carbohydrate antigen sialyl-Tn (STn) in breast cancer is associated with a poor prognosis; however, involvement of STn in the development of metastatic bone lesions remains unclear. We investigated whether STn expression on breast cancer cells influences intraosseous tumor growth and bone response in mice models of skeletal colonization. STn-positive (STn+) breast cancer cells were generated by stable transfection of an expression vector encoding ST6GaLNAc I into the breast cancer cell line MDA-MB-231. Parental MDA-MB-231 cells not expressing STn antigen were used as STn-negative (STn-) breast cancer cells. Contrary to expectations, STn expression attenuated the development of destructive bone lesions in the in vivo mice models. An in vitro study demonstrated that STn expression impaired adhesion of MDA-MB-231cells to bone marrow stromal cells. This finding in vitro was also confirmed by another breast cancer cell line MCF-7. Cell adhesion to fibronectin and type I collagen was also impaired in STn+ MDA-MB-231 cells compared to that in STn- MDA-MB-231 cells, suggesting integrin dysfunction. Given that the integrin β1 subunit is the main carrier of the STn epitope, it is likely that changes in glycan structure impaired the adhesive capacity of β1 integrin in the bone environment, leading to attenuation of tumor cell engraftment. In conclusion, breast cancer cells expressing STn antigen had less capacity for skeletal colonization, possibly due to impaired adhesive capability.