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Updated: Aug 27, 2026
Orthotopic Xenografting of Human Luciferase-Tagged Malignant Peripheral Nerve Sheath Tumor Cells for in vivo Testing of Candidate Therapeutic Agents
Published on: March 7, 2011
Effects of all-trans retinoic acid and interferon alpha in peripheral neuroectodermal tumor cell cultures and
A Rosolen1, G Favaretto, G Masarotto
1Divisione di Emato-Oncologia Pediatrica, Dipartimento di Pediatria, Universita di Padova, 35128 Padova, Italy.
Abstract:
Peripheral neuroectodermal tumors (PNET) have an unsatisfactory outcome when treated with standard approaches. Among novel treatments, the use of biological response modifiers has rarely been reported in this group of malignancies. We have previously demonstrated that both all-trans retinoic acid (ATRA) and interferon á (IFNá) can inhibit proliferation of human PNET cells and that ATRA can up-regulate IFNá receptor expression in vitro. In this study we evaluated the anti-tumor effects of ATRA and IFNá in PNET cells in vitro and in a human PNET xenograft model, using CHP100 cells. A synergistic inhibitory effect of ATRA and IFNá was observed on CHP100 cells in vitro. On the contrary, a significant inhibition of tumor growth was observed in mice treated with ATRA alone, whereas neither IFNá nor the combination of ATRA and IFNá, reached a statistically significant anti-tumor effect. Histologic examination of tumors revealed the presence of necrosis upon treatment with IFNá, whereas almost no necrosis, but a more differentiated morphology, confirmed by electron microscopy analysis, was associated with the ATRA containing treatments. Taken together these data show an in vitro and in vivo anti-tumor activity of ATRA in human PNET cells, although no synergism of ATRA and IFNá was observed in our xenograft model.
Insights
All-trans retinoic acid (ATRA) shows anti-tumor activity in peripheral neuroectodermal tumors (PNET) models. Combination therapy with interferon-alfa (IFNα) demonstrated synergistic effects in vitro but not in vivo.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Peripheral neuroectodermal tumors (PNET) exhibit poor outcomes with standard treatments.
- Biological response modifiers are infrequently reported for PNET malignancies.
- Previous studies indicated all-trans retinoic acid (ATRA) and interferon-alfa (IFNα) inhibit PNET cell proliferation, with ATRA upregulating IFNα receptor expression.
Purpose of the Study:
- To evaluate the anti-tumor effects of ATRA and IFNα in human PNET cells and a xenograft model.
- To assess the potential synergistic interaction between ATRA and IFNα in PNET treatment.
Main Methods:
- In vitro studies using CHP100 PNET cells to assess proliferation inhibition.
- In vivo studies using a human PNET xenograft model in mice.
- Histological examination and electron microscopy to evaluate tumor morphology and differentiation.
Main Results:
- A synergistic inhibitory effect of ATRA and IFNα was observed on CHP100 cells in vitro.
- ATRA monotherapy significantly inhibited tumor growth in the xenograft model.
- IFNα alone or in combination with ATRA did not achieve statistically significant tumor growth inhibition.
- ATRA treatment led to more differentiated tumor morphology, while IFNα induced necrosis.
Conclusions:
- ATRA demonstrates in vitro and in vivo anti-tumor activity against human PNET cells.
- The synergistic anti-tumor effect observed in vitro between ATRA and IFNα was not replicated in the in vivo xenograft model.
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