Targeting the αVβ3/NgR2 pathway in neuroendocrine prostate cancer

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; Liu, Qin; Ding, Jianyi; Kelly, William K.; Hooper, D. Craig; Corey, Eva; Plow, Edward F.; Altieri, Dario C.; Languino, Lucia R.

doi:10.1016/j.matbio.2023.11.003

Cited by 2 publications

(3 citation statements)

References 74 publications

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“…EV isolation by differential ultracentrifugation of healthy donor and diagnosed PRAD patient plasma was performed as previously described. 31 , 49 , 50 …”

Section: Methodsmentioning

confidence: 99%

“…NTA was performed as previously described. 50 , 51 Briefly, pooled plasma sEVs (fractions 6–8) were diluted in PBS and analyzed using NanoSight NS300. A total of three videos (30 seconds each) were captured.…”

Section: Methodsmentioning

confidence: 99%

“…IB analysis was performed as previously described. 50–52 For IB, sEVs and cells were lysed using RIPA buffer (10 mM Tris-HCl, pH 7.4, 150 mM NaCl, 1 mM EDTA, 0.1% SDS, 1% NP-40, and 1% sodium deoxycholate) and protease inhibitors were added. The following primary rabbit Ab was used: Syntenin (Abcam, ab133267).…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Neuroendocrine gene subsets are uniquely dysregulated in prostate adenocarcinoma

Naranjo,

Kennedy,

Testa

et al. 2024

Cancer Biology & Therapy

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“…EV isolation by differential ultracentrifugation of healthy donor and diagnosed PRAD patient plasma was performed as previously described. 31 , 49 , 50 …”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Neuroendocrine gene subsets are uniquely dysregulated in prostate adenocarcinoma

Naranjo,

Kennedy,

Testa

et al. 2024

Cancer Biology & Therapy

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Expression of the αVβ3 integrin affects prostate cancer sEV cargo and density and promotes sEV pro‐tumorigenic activity in vivo through a GPI‐anchored receptor, NgR2

Verrillo,

Quaglia,

Shields

et al. 2024

J of Extracellular Vesicle

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It is known that small extracellular vesicles (sEVs) are released from cancer cells and contribute to cancer progression via crosstalk with recipient cells. We have previously reported that sEVs expressing the αVβ3 integrin, a protein upregulated in aggressive neuroendocrine prostate cancer (NEPrCa), contribute to neuroendocrine differentiation (NED) in recipient cells. Here, we examine the impact of αVβ3 expression on sEV protein content, density and function. sEVs used in this study were isolated by iodixanol density gradients and characterized by nanoparticle tracking analysis, immunoblotting and single vesicle analysis. Our proteomic profile of sEVs containing αVβ3 shows downregulation of typical effectors involved in apoptosis and necrosis and an upregulation of tumour cell survival factors compared to control sEVs. We also show that the expression of αVβ3 in sEVs causes a distinct reposition of EV markers (Alix, CD81, CD9) to a low‐density sEV subpopulation. This low‐density reposition is independent of extracellular matrix (ECM) protein interactions with sEVs. This sEV subset contains αVβ3 and an αVβ3 downstream effector, NgR2, a novel marker for NEPrCa. We show that sEVs containing αVβ3 are loaded with higher amounts of NgR2 as compared to sEVs that do not express αVβ3. Mechanistically, we demonstrate that sEVs containing NgR2 do not affect the sEV marker profile, but when injected in vivo intratumorally, they promote tumour growth and induce NED. We show that sEVs expressing NgR2 increase the activation of focal adhesion kinase (FAK), a known promoter of cancer cell proliferation, in recipient cells. We also show that NgR2 mimics the effect of sEVs containing αVβ3 since it displays increased growth of NgR2 transfectants in vivo, as compared to control cells. Overall, our results describe the changes that occur in cargo, density and functions of cancer cell‐derived sEVs containing the αVβ3 integrin and its effector, NgR2, without affecting the sEV tetraspanin profiles.

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Targeting the αVβ3/NgR2 pathway in neuroendocrine prostate cancer

Cited by 2 publications

References 74 publications

Neuroendocrine gene subsets are uniquely dysregulated in prostate adenocarcinoma

Neuroendocrine gene subsets are uniquely dysregulated in prostate adenocarcinoma

Expression of the αVβ3 integrin affects prostate cancer sEV cargo and density and promotes sEV pro‐tumorigenic activity in vivo through a GPI‐anchored receptor, NgR2

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