P2Y2R has a significant correlation with Notch-4 in patients with breast cancer

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.

Keywords: CD44; CSC markers; Notch-4; Oct3/4; P2Y2 receptor; breast cancer.

Figure 1.

CD44, Oct3/4 and Notch-4 cancer stem cell markers are significantly expressed in the tumor tissues compared with normal epithelial tissues of patients with breast cancer. The expression levels of cancer stem cell markers (CD24, CD44, Oct3/4, Notch-4 and ALDH1A1) were compared in normal epithelial tissues (n=20) and tumor tissues (n=180) of patients with breast cancer (n=180). ALDH, aldehyde dehydrogenase.

Figure 2.

P2Y₂R, which is also significantly expressed in the tumor tissues of breast cancer patients, correlates only with Notch-4, of the cancer stem cell markers. (A) P2Y₂R expression is significantly increased in the tumor tissue (n=180) compared with normal epithelial tissue (n=20) of patients with breast cancer (n=180). (B) P2Y₂R expression has a significant correlation with Notch-4 cancer stem cell marker in patients with breast cancer. (C) Immunohistochemical staining of P2Y₂R and Notch-4 in tumor tissues and normal epithelial tissues of patients with breast cancer.