Targeting the αvβ3/NGR2 Pathway in Neuroendocrine Prostate Cancer

Authors

Anna Testa, Thomas Jefferson UniversityFollow
Fabio Quaglia, Thomas Jefferson UniversityFollow
Nicole M. Naranjo, Thomas Jefferson UniversityFollow
Cecilia E. Verrillo, Thomas Jefferson UniversityFollow
Christopher D. Shields, Thomas Jefferson UniversityFollow
Stephen Lin, Thomas Jefferson University
Maxwell W. Pickles, Thomas Jefferson UniversityFollow
Drini F. Hamza, Thomas Jefferson UniversityFollow
Tami Von Schalscha
David A. Cheresh
Benjamin E Leiby, Thomas Jefferson UniversityFollow
Qin Liu
Jianyi Ding
William K. Kelly, Thomas Jefferson UniversityFollow
D. Craig Hooper, Thomas Jefferson UniversityFollow
Eva Corey
Edward F. Plow
Dario C. Altieri
Lucia R. Languino, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

11-11-2023

Comments

This article is the author's final published version in Matrix Biology, Volume 124, December 2023, Pages 49-62.

The published version is available at https://doi.org/10.1016/j.matbio.2023.11.003. Copyright © 2023 The Authors. Published by Elsevier B.V.

Abstract

Highly aggressive, metastatic, neuroendocrine prostate cancer, which typically develops from prostate cancer cells acquiring resistance to androgen deprivation therapy, is associated with limited treatment options and hence poor prognosis. We have previously demonstrated that the αVβ3 integrin is over-expressed in neuroendocrine prostate cancer. We now show that LM609, a monoclonal antibody that specifically targets the human αVβ3 integrin, hinders the growth of neuroendocrine prostate cancer patient-derived xenografts in vivo. Our group has recently identified a novel αVβ3 integrin binding partner, NgR2, responsible for regulating the expression of neuroendocrine markers and for inducing neuroendocrine differentiation in prostate cancer cells. Through in vitro functional assays, we here demonstrate that NgR2 is crucial in promoting cell adhesion to αVβ3 ligands. Moreover, we describe for the first time co-fractionation of αVβ3 integrin and NgR2 in small extracellular vesicles derived from metastatic prostate cancer patients' plasma. These prostate cancer patient-derived small extracellular vesicles have a functional impact on human monocytes, increasing their adhesion to fibronectin. The monocytes incubated with small extracellular vesicles do not show an associated change in conventional polarization marker expression and appear to be in an early stage that may be defined as "adhesion competent". Overall, these findings allow us to better understand integrin-directed signaling and cell-cell communication during cancer progression. Furthermore, our results pave the way for new diagnostic and therapeutic perspectives for patients affected by neuroendocrine prostate cancer.

Recommended Citation

Testa, Anna; Quaglia, Fabio; Naranjo, Nicole M.; Verrillo, Cecilia E.; Shields, Christopher D.; Lin, Stephen; Pickles, Maxwell W.; Hamza, Drini F.; Von Schalscha, Tami; Cheresh, David A.; Leiby, Benjamin E; Liu, Qin; Ding, Jianyi; Kelly, William K.; Hooper, D. Craig; Corey, Eva; Plow, Edward F.; Altieri, Dario C.; and Languino, Lucia R., "Targeting the αvβ3/NGR2 Pathway in Neuroendocrine Prostate Cancer" (2023). Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers. Paper 7.
https://jdc.jefferson.edu/ppcbfp/7

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Language

English