Level C· Early human research exploring benefitsProspective StudyEurope PMCOpen access

NGF-mediated tumor-stroma crosstalk promotes prostate cancer aggressiveness

Di Donato M., Giovannelli P., De Sio M., Migliaccio A., Castoria G.

Prospective Study, published in J Transl Med (2026) — summary generated from the PubMed abstract.

Open my reading list
Level C· Early human research exploring benefitsEvidence level of this study

Early human evidence such as case series or small samples is exploring possible benefits.

  • Level A · Stronger Clinical Evidence
  • Level B · Emerging clinical evidence with positive signals
  • Level C · Early human research exploring benefits
  • Level D · Scientific groundwork from lab and animal studies
  • Emerging · Emerging topic under active research
Read the A–D evidence level guide

This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.

Study type
Prospective Study
Journal
J Transl Med (2026)
Reported sample size
—
Source database
Europe PMC
PMID
41742295
PMCID
PMC12980896
DOI
10.1186/s12967-026-07915-7

Abstract (original English)

BACKGROUND: Nerve growth factor (NGF) is involved in prostate cancer (PC) pathogenesis and progression. Nevertheless, its source and its role in tumor microenvironment remain still unclear as well as its contribution to tumor–stroma interactions. METHODS: Single-cell transcriptomics analysis from multiple PC datasets was performed to identify the NGF-expressing cell populations. Primary cancer-associated fibroblasts (CAFs) isolated from PC patient’s specimens were analyzed for NGF secretion and expression of the NGF receptor, TrkA. 3D tumor-stroma co-cultures were used to investigate the NGF-mediated interactions between CAFs and epithelial PC cells. Migration, invasion, and perineural invasion (PNI) assays were done to evaluate the functional outcomes, alongside the pharmacological and antibody-based inhibition of NGF/TrkA axis. RESULTS: High NGF expression correlates with reduced disease-free survival in PC patients. Single-cell analyses reveal that stromal fibroblasts and myofibroblasts are the main sources of NGF within the PC microenvironment. Primary CAFs secrete NGF and express TrkA, supporting the existence of an autocrine signaling loop. In 3D co-cultures, NGF promotes CAF spatial organization around tumor spheroids, increases spheroid size, and induces EMT-like changes in epithelial PC cells. CAF-derived NGF further stimulates directional migration and invasion in bot

What this study does not prove

  • • This study does not prove SVF is an approved treatment or a replacement for standard care.

Evidence level

Early human evidence such as case series or small samples is exploring possible benefits.

How we grade evidence
Cell Line, TumorSpheroids, CellularStromal CellsHumansProstatic NeoplasmsNeoplasm InvasivenessReceptor, trkANerve Growth FactorCoculture TechniquesCell Communication

Browse all related research

Filter the research library by this study's title keywords, author, or publication year.