N-Myc promotes angiogenesis and therapeutic resistance of prostate cancer by TEM8

Mingfeng Li,Linna Fang,Yuhang Huang,Li Zhang,Zhuting Tong,Shiyuan Yin,Lijie Yang,Wei Ma,Louis Boafo Kwantwi,Yu Yin,Chaozhao Liang,Yongping Cai,Wenwu Luo,Heqin Zhan,Guifang He

doi:10.1007/s12032-021-01575-x

Abstract

Although patients with early localized prostate cancer can survive longer, castration-resistant prostate cancer (CRPC) has gradually emerged with the use of androgen deprivation therapy (ADT). N-Myc and TEM8 play a vital role in the progression of several cancer types. However, the underlying mechanism of how N-Myc and TEM8 promote the progression of prostate cancer remains unclear. In this study, the expression of N-Myc and TEM8 was detected in benign prostatic hyperplasia (BPH) and prostate cancer (PCa) tissues by immunohistochemistry (IHC). LNCaP cell lines were maintained in RPMI 1640 medium supplemented with 10% charcoal-stripped fetal bovine serum. Subsequently, R language software was used to verify our results. Tubule formation assay of human umbilical vein endothelial cell (HUVEC) was conducted to examine the effect of N-Myc and TEM8 overexpression on angiogenesis in prostate cancer cells. IHC results showed a positive correlation between the expression of N-Myc and TEM8 in prostate cancer tissues. Further analysis showed that N-Myc and TEM8 were associated with clinicopathological features and poor prognosis in prostate cancer patients. Moreover, the overexpression of N-Myc and TEM8 promoted proliferation of prostate cancer cells and angiogenesis. Additionally, N-Myc and TEM8 overexpression was associated with therapeutic resistance. We further found that N-Myc promoted angiogenesis and therapeutic resistance in prostate cancer via TEM8. Hence, targeting N-Myc/TEM8 pathway in prostate cancer would be a novel therapeutic strategy to enhance the treatment of prostate cancer patients.

Highlights

Prostate cancer (PCa) is the most diagnosed malignancy in men and the second leading cause of cancer-related deaths in the USA
IHC results showed that the positive rate of N-Myc and TEM8 was significantly higher in PCa than in benign prostatic hyperplasia (BPH) samples (Fig. 1A–D; Table 1)
N-Myc and TEM8 expressions are closely related to the clinical progression and prognosis of prostate cancer

Summary

Introduction

Prostate cancer (PCa) is the most diagnosed malignancy in men and the second leading cause of cancer-related deaths in the USA. Medical Oncology (2021) 38:127 options has significantly reduced the incidence rate, there has been a steady increase in advanced or metastasized prostate cancers [1]. The symptoms of prostate cancer in the early stage are not evident in most cases, which makes treatment more difficult [2]. The advent usage of androgen deprivation therapy (ADT) has brought some symptomatic relief to prostate cancer patients. This leads to the development of castration-resistant prostate cancer. A deeper understanding of the mechanism of the disease process is relevant in our quest to find a novel and specific biomarker for prostate cancer treatment

Methods

Results

Conclusion