Neuropilin-2 axis in regulating secretory phenotype of neuroendocrine-like prostate cancer cells and its implication in therapy resistance

Ridwan Islam, Juhi Mishra, Navatha Shree Polavaram, Sreyashi Bhattacharya, Zhengdong Hong, Sanika Bodas, Sunandini Sharma, Alyssa Bouska, Tyler Gilbreath, Ahmed M. Said, Lynette M. Smith, Benjamin A. Teply, Michael H. Muders, Surinder K. Batra, Kaustubh Datta, Samikshan Dutta

Research output: Contribution to journalArticlepeer-review

Abstract

Neuroendocrine (NE)-like tumors secrete various signaling molecules to establish paracrine communication within the tumor milieu and to create a therapy-resistant environment. It is important to identify molecular mediators that regulate this secretory phenotype in NE-like cancer. The current study highlights the importance of a cell surface molecule, Neuropilin-2 (NRP2), for the secretory function of NE-like prostate cancer (PCa). Our analysis on different patient cohorts suggests that NRP2 is high in NE-like PCa. We have developed cell line models to investigate NRP2’s role in NE-like PCa. Our bioinformatics, mass spectrometry, cytokine array, and other supporting experiments reveal that NRP2 regulates robust secretory phenotype in NE-like PCa and controls the secretion of factors promoting cancer cell survival. Depletion of NRP2 reduces the secretion of these factors and makes resistant cancer cells sensitive to chemotherapy in vitro and in vivo. Therefore, targeting NRP2 can revert cellular secretion and sensitize PCa cells toward therapy.

Original languageEnglish (US)
Article number111097
JournalCell Reports
Volume40
Issue number3
DOIs
StatePublished - Jul 19 2022

Keywords

  • CP: Cancer
  • IL8
  • VAMP2
  • neuroendocrine
  • neuropilin-2
  • prostate cancer
  • secretion
  • synapsin-1

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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