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Nerve growth factor and retinoic acid inhibit proliferation and invasion in thyroid tumor cells
M Páez Pereda1, C Missale, Y Grübler
1Max Planck Institute of Psychiatry, Department of Endocrinology, Kraepelinstr. 10, 80804, Munich, Germany. marcelo@mpipsykl.mpg.de
Abstract:
NGF has anti-proliferative and anti-invasive effects in neuroendocrine tumors. In the present work we examined the effects of NGF and retinoic acid on cell proliferation and invasion in thyroid carcinoma cells. We found that NGF and retinoic acid do not affect cell proliferation on their own but in combination they produce a strong inhibition. We also found that retinoic acid regulates the matrix metalloproteinase 2 activity and invasion. In contrast, NGF inhibited invasion and reverted the effect of retinoic acid. This effect of NGF is likely mediated by an increase in adhesion to laminin and collagen IV and the inhibition of cell migration. NGF also induced the expression of the p75 NGF receptor. In conclusion, NGF and retinoic acid in combination inhibit proliferation and invasion of thyroid papillary carcinoma cells. These data open the possibility of a potential combined therapy for thyroid papillary carcinomas.
Insights
Nerve growth factor (NGF) and retinoic acid combined strongly inhibit thyroid papillary carcinoma cell proliferation and invasion. This combination therapy shows potential for treating thyroid cancer.
Area of Science:
- Oncology
- Cell Biology
- Molecular Medicine
Background:
- Neuroendocrine tumors exhibit anti-proliferative and anti-invasive responses to Nerve Growth Factor (NGF).
- Thyroid carcinoma presents a significant challenge in cancer treatment, necessitating novel therapeutic strategies.
Purpose of the Study:
- To investigate the combined effects of NGF and retinoic acid on thyroid carcinoma cell proliferation and invasion.
- To elucidate the molecular mechanisms underlying NGF's influence on thyroid cancer cell behavior.
Main Methods:
- Cell proliferation and invasion assays were performed on thyroid carcinoma cells.
- Matrix metalloproteinase 2 (MMP-2) activity was assessed.
- Cell adhesion to laminin and collagen IV, and cell migration were evaluated.
- Expression of the p75 NGF receptor was analyzed.
Main Results:
- NGF and retinoic acid synergistically inhibited thyroid carcinoma cell proliferation.
- Retinoic acid alone increased MMP-2 activity and invasion; NGF counteracted these effects.
- NGF enhanced cell adhesion to laminin and collagen IV, inhibiting cell migration.
- NGF treatment upregulated p75 NGF receptor expression.
Conclusions:
- Combined NGF and retinoic acid treatment effectively inhibits proliferation and invasion in thyroid papillary carcinoma cells.
- NGF's anti-invasive action is mediated by increased cell adhesion and reduced migration.
- These findings suggest a potential therapeutic strategy using combined NGF and retinoic acid for thyroid papillary carcinomas.