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Updated: May 16, 2026
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
NGAL controls the metastatic potential of anaplastic thyroid carcinoma cells
Vincenzo Volpe1, Zelinda Raia, Luca Sanguigno
1Dipartimento di Biologia e Patologia Cellulare e Molecolare, Federico II University of Naples, 80131 Naples, Italy.
Context:
We have previously identified neutrophil gelatinase-associated lipocalin (NGAL) as one of the genes mediating the oncogenic activity of nuclear factor-κB in human anaplastic thyroid carcinomas (ATCs).
Objectives:
To further investigate the role of NGAL in thyroid cancer, we established NGAL knocked-down and NGAL overexpressing ATC cell lines.
Results:
We found that the ability of NGAL knocked-down cells to degrade Matrigel in a transwell invasion assay and to form lung metastasis in nude mice was decreased. Because NGAL binds matrix metalloproteinase-9 (MMP-9), to form a macromolecular complex involved in the regulation of metastatic spread of cancer cells and given the strong expression of both genes in tissue specimens from human ATCs, we analyzed the MMP-9 enzymatic activity in NGAL-null ATC cells. Enzymatic immunoassays show that MMP-9 activity is reduced in NGAL-null ATC cells, even if its expression is not affected by NGAL inhibition. Ectopic expression of NGAL in an ATC cell line not expressing NGAL determines an increase of its metastatic property. The use of a mutated form of NGAL, unable to bind MMP-9, has no positive effect on the invasive potential of ATC cells and does not improve the MMP-9 enzymatic activity.
Conclusions:
Our results indicate NGAL as a novel target of nuclear factor-κB prometastatic activity in thyroid cancer through enhancement of MMP-9 enzymatic activity.
Insights
Neutrophil gelatinase-associated lipocalin (NGAL) promotes thyroid cancer metastasis by enhancing matrix metalloproteinase-9 (MMP-9) activity. Inhibiting NGAL reduces cancer cell invasion and spread. NGAL is a key target for controlling thyroid cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Neutrophil gelatinase-associated lipocalin (NGAL) is implicated in the oncogenic functions of nuclear factor-κB in anaplastic thyroid carcinomas (ATCs).
- Understanding NGAL's role is crucial for developing targeted therapies for thyroid cancer.
Purpose of the Study:
- To investigate the specific role of NGAL in thyroid cancer progression.
- To elucidate the molecular mechanisms by which NGAL influences cancer cell metastasis.
Main Methods:
- Generation of anaplastic thyroid carcinoma (ATC) cell lines with NGAL knockdown and overexpression.
- In vitro Matrigel degradation and transwell invasion assays.
- In vivo lung metastasis assays in nude mice.
- Analysis of matrix metalloproteinase-9 (MMP-9) activity using enzymatic immunoassays.
Main Results:
- NGAL knockdown significantly decreased cancer cell invasion and lung metastasis formation.
- MMP-9 enzymatic activity was reduced in NGAL-null ATC cells, independent of MMP-9 expression levels.
- Overexpression of NGAL enhanced the metastatic potential of ATC cells.
- A mutated form of NGAL, unable to bind MMP-9, did not restore invasive potential, highlighting the importance of the NGAL-MMP-9 interaction.
Conclusions:
- NGAL enhances the enzymatic activity of MMP-9, thereby promoting thyroid cancer metastasis.
- NGAL acts as a novel mediator of nuclear factor-κB's prometastatic activity in thyroid cancer.
- Targeting NGAL presents a potential therapeutic strategy for inhibiting thyroid cancer progression.
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