CD155 downregulation synergizes with adriamycin to induce breast cancer cell apoptosis

Jian Gao,Wei Wang,Yue Shao,Chenghai Zhao,Qianqian Zheng

doi:10.1007/s10495-018-1473-8

Abstract

CD155 has been implicated in migration, invasion, proliferation and apoptosis of human cancer cells, and DNA damage response caused by chemotherapeutic agents or reactive oxygen species has been shown to attribute to CD155 induction. Adriamycin (Adr) is one of the most common chemotherapeutic drugs used to treat breast cancer. Here we reported that treatment with Adr upregulated CD155 expression on several in vitro cultured breast cancer cells and in breast cancer cell 4T1 xenografts. We also found that CD155 knockdown or Adr treatment induced apoptosis of in vitro cultured cancer cells and cancer cells in 4T1 xenografts, and a combination of CD155 knockdown with Adr treatment induced more cell death than either of them. Furthermore, we revealed that the combination of CD155 knockdown with Adr treatment suppressed the growth of 4T1 xenografts more significantly than them alone. In summary, our results demonstrate that CD155 downregulation synergizes with Adr to induce breast cancer cell apoptosis, thereby to suppress tumor growth. Our results also suggest that CD155 upregulation may be a mechanism underlying Adr resistance by breast cancer cells.

Highlights

Due to functioning as the receptor for poliovirus, and harboring domain structures similar to nectins, CD155 is called PVR [1] and nectin-like protein 5 [2]
As shown by Western blot detection, CD155 expression was significantly upregulated in these CD155-treated cancer cells compared with CD155-untreated cells (Fig. 1a)
CD155 induction by Adr treatment was further confirmed by immunofluorescence staining in these human and mouse breast cancer cells (Fig. 1b)

Summary

Introduction

Due to functioning as the receptor for poliovirus, and harboring domain structures similar to nectins, CD155 is called PVR [1] and nectin-like protein 5 (necl-5) [2]. CD155 expression is undetected in most normal tissues, while upregulated in Ras or Src-transformed NIH3T3 cells [5] and several human cancers [7,8,9]. CD155 expression can be induced by DNA damage. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) stimulate CD155 expression through DNA damage response (DDR) [17, 18]. Chemotherapeutic agents induce CD155 expression on multiple myeloma cells through DDR [19]. Given the positive role of CD155 in tumor growth, in the present study we asked whether Adriamycin (Adr) treatment [20,21,22] could upregulate CD155 expression in breast cancer cells, and whether CD155 knockdown could affect Adr-induced breast cancer cell apoptosis

Methods

Results

Conclusion