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Updated: Aug 18, 2026

Orthotopic Implantation and Peripheral Immune Cell Monitoring in the II-45 Syngeneic Rat Mesothelioma Model
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Orthotopic Implantation and Peripheral Immune Cell Monitoring in the II-45 Syngeneic Rat Mesothelioma Model

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Gremlin-1 is a key regulator of the invasive cell phenotype in mesothelioma

Miao Yin1,2, Mira Tissari1,2, Jenni Tamminen1,2

  • 1Research Programs Unit, Translational Cancer Biology, University of Helsinki, Helsinki, Finland.

Oncotarget
|December 13, 2017
PubMed

Insights

Gremlin-1 promotes mesothelioma cell invasion and metastasis by inducing a mesenchymal phenotype and enhancing tumor vascularization. Targeting Gremlin-1 may offer a new therapeutic strategy for this aggressive cancer.

Area of Science:

  • Oncology
  • Cancer Biology
  • Molecular Medicine

Background:

  • Malignant mesothelioma is an aggressive cancer with poor prognosis and limited treatment options.
  • Gremlin-1 is a protein known to inhibit BMP-pathway activity and has been found at high levels in mesothelioma tissue.

Purpose of the Study:

  • To investigate the role of Gremlin-1 in mesothelioma cell migration and invasive growth.
  • To identify potential therapeutic targets for malignant mesothelioma.

Main Methods:

  • Studied Gremlin-1's effect on mesothelioma cell invasion in 3D collagen and Matrigel matrices.
  • Analyzed the expression of SNAI2, integrins, matrix metalloproteinases (MMPs), and TGF-β signaling.
  • Utilized small molecule inhibitors of MMPs and TGF-β receptors.
  • Conducted in vivo mesothelioma xenograft experiments.

Main Results:

  • Gremlin-1 significantly promoted mesothelioma cell sprouting and invasion.
  • Gremlin-1 expression correlated with changes in SNAI2, integrins, MMPs, and TGF-β signaling.
  • MMP inhibitors blocked invasive growth, while TGF-β receptor inhibitors reduced it, indicating dual mechanisms.
  • In vivo studies showed Gremlin-1 overexpression led to increased tumor vascularization and metastasis.

Conclusions:

  • Gremlin-1 drives mesothelioma invasion and metastasis by promoting a mesenchymal phenotype and enhancing tumor vascularization.
  • Gremlin-1 represents a potential therapeutic target for malignant mesothelioma.
Keywords:
gremlininvasionmesothelioma

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