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Updated: Jan 11, 2026

A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth
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Fibroblast activation protein (FAP)-mediated promotion of metastasis via the FN1-TGFβ axis and immune suppression in

Mario Udinotti1, Udo Siebolts1,2, Marcus Bauer1

  • 1Institute of Pathology, Martin Luther University Halle-Wittenberg, Halle, Germany.

Journal of Translational Medicine
|November 13, 2025
PubMed
Abstract

Insights

Fibroblast activation protein (FAP) promotes aggressive thyroid carcinoma (TC) by altering the tumor microenvironment and immune evasion. Targeting FAP may improve treatment outcomes for patients with advanced TC.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Aggressive thyroid carcinoma (TC) has limited treatment options due to its aggressiveness.
  • Tumor-intrinsic immune escape mechanisms and the tumor microenvironment contribute to metastasis in TC.
  • Extracellular matrix (ECM) components, cancer-associated fibroblasts (CAFs), and fibroblast activation protein (FAP) are implicated in immune evasion, disease progression, and poor prognosis in TC.

Purpose of the Study:

  • To investigate the role of FAP in aggressive thyroid carcinoma.
  • To explore the relationship between FAP, tumor microenvironment, and immune cell infiltration in TC.
  • To assess FAP as a potential therapeutic target for aggressive TC.

Main Methods:

  • Analysis of The Cancer Genome Atlas (TCGA) and Human Protein Atlas datasets for TC specimens.
  • Examination of 187 TC samples using tissue microarrays (TMA) for marker expression and immune cell infiltration.
  • In vitro studies involving TC cell lines treated with FAP modulators and co-cultured with CAFs, analyzed by qPCR, Western blot, flow cytometry, ELISA, and immunohistochemistry (IHC).

Main Results:

  • High FAP and fibronectin 1 (FN1) expression correlated positively with metastatic parameters and CD8+ T cell infiltration in TC.
  • FAP cleaved FN1, leading to reduced adhesion, increased invasion, and inhibition of transforming growth factor beta (TGF-β).
  • FAP influenced immune suppressive CAF subtypes, reduced PD-L1, and increased HLA-ABC surface levels.

Conclusions:

  • FAP-mediated alterations in ECM, TC cells, and CAFs highlight its role in tumor immunogenicity, immune infiltration, and metastasis.
  • FAP is a promising therapeutic target for aggressive thyroid carcinoma (ATC).
  • FAP serves as a powerful marker for predicting immune infiltration and metastatic potential in TC.
Keywords:
Cancer associated fibroblastsExtracellular matrix componentsFibroblast activating proteinImmune escapeInvasionThyroid cancerTumor microenvironment

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