경상대 / 김동철, 진하나, 이경원*, 김혜정*
Abstract
Our previous study found that highly metastatic breast cancer cells, such as MDA-MB-231 cells, release higher levels of ATP and exhibit greater P2Y2 receptor (P2Y2R) activity than lowly metastatic breast cancer cells, and that P2Y2R activation mediated by ATP plays a significant role in tumor progression and metastasis. In addition, we reported that radiotherapy-resistant (RT-R) breast cancer cells promote invasion and tumor growth through the activation of P2Y2R by ATP released from RT-R-breast cancer cells than breast cancer cells. Moreover, increased numbers of cancer stem cells (CSCs) were observed among the RT-R-breast cancer cell population. Therefore, in this study, we investigated the expression level of five CSC markers (CD24, CD44, Oct3/4, Notch-4 and ALDH1A1) as well as P2Y2R in the tumor tissues of patients with breast cancer and determined which CSC marker correlates with P2Y2R in breast cancer. According to the immunohistochemical analysis, CD44, Oct3/4 and Notch-4 but not ALDH1A1 were significantly expressed in the tumor tissues (n=180) compared with the normal epithelial tissues (n=20) of patients with breast cancer. It was demonstrated that P2Y2R expression was increased in tumor tissues of patients with breast cancer compared with normal epithelial tissue. Notably, it was identified that P2Y2R expression has a significant correlation with only the CSC marker Notch-4 in patients with breast cancer. The results of this study suggested for the first time to the best of our knowledge that Notch-4 has a notable correlation with P2Y2R, which has important roles in tumor progression and metastasis.
Affiliations
Dong Chul Kim 1 , Hana Jin 2 , Jong Sil Lee 1 , Euna Son 3 , Gyeong Won Lee 4 , Hye Jung Kim 2
1 Department of Pathology, College of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju, South Gyeongsang 52727, Republic of Korea.
2 Department of Pharmacology, College of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju, South Gyeongsang 52727, Republic of Korea.
3 Division of Life Science, College of Natural Sciences, Gyeongsang National University, Jinju, South Gyeongsang 52828, Republic of Korea.
4 Division of Hematology-Oncology, Department of Internal Medicine, College of Medicine, Gyeongsang National University Hospital, Gyeongsang National University, Jinju, South Gyeongsang 52727, Republic of Korea.