PSMA-positive membranes secreted from prostate cancer cells have potency to transform vascular endothelial cells into an angiogenic state

Ryuta Watanabe, Masashi Maekawa, Takeshi Kiyoi, Mie Kurata, Noriyoshi Miura, Tadahiko Kikugawa, Shigeki Higashiyama, Takashi Saika

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Prostate-specific membrane antigen (PSMA) is highly expressed in poorly differentiated, metastatic, and castration-resistant prostate cancers. Recently, 68Ga-PSMA positron emission tomography/computed tomography has been successfully developed as an effective diagnostic tool for prostate cancer. However, the pathophysiological functions of PSMA in prostate tumors remain unclear. Methods: We examined the protein expression of PSMA in tumor endothelial cells in human prostate tumors by immunohistochemistry. Prostate cancer tissues were resected by robotic surgery in 2019 at Ehime University from patients with prostate cancer. In vitro, we prepared conditioned medium (CM) derived from a PSMA-positive human prostate cancer cell line, LNCaP, cultured on collagen I gels. We then examined PSMA expression in human umbilical vascular endothelial cells (HUVECs) cultured with the CM. We assessed angiogenic activities by treatment of HUVECs with LNCaP-derived CM using a tube formation assay that mimics angiogenesis. Results: Immunohistochemistry of PSMA and CD31, a marker of endothelial cells, and PSMA-expressing tumor endothelial cells were observed in 4 of 33 prostate cancer patients (12.1%). We also found that the 10,000g pellet fraction of the LNCaP-derived CM containing PSMA-positive membranes, such as microvesicles transformed HUVECs “PSMA-negative” into “PSMA-positive.” Furthermore, treatment of HUVECs with the 10,000g pellet fraction of the LNCaP-derived CM significantly promoted tube formation, mimicking angiogenesis in a PSMA-dependent manner. Conclusions: Our findings revealed the existence of PSMA-positive tumor endothelial cells in human prostate tumors, which enhances tumor angiogenesis in prostate cancer tissues.

Original languageEnglish
Pages (from-to)1390-1401
Number of pages12
JournalProstate
Volume81
Issue number16
DOIs
Publication statusPublished - 2021 Dec 1
Externally publishedYes

Keywords

  • LNCaP
  • human umbilical vascular endothelial cells (HUVECs)
  • prostate cancer specimen
  • prostate-specific membrane antigen (PSMA)
  • tube formation
  • tumor endothelial cells

ASJC Scopus subject areas

  • Oncology
  • Urology

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