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A Model for Perineural Invasion in Head and Neck Squamous Cell Carcinoma
Published on: January 5, 2017
Radiation impairs perineural invasion by modulating the nerve microenvironment.
Richard L Bakst1, Nancy Lee, Shuangba He
1Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
Plos One
|July 7, 2012
Summary
Radiation therapy can inhibit cancer cell perineural invasion (PNI) by directly impacting cancer cells or by altering nerve microenvironment factors like GDNF. This suggests new therapeutic strategies for cancers with PNI.
Area of Science:
- Oncology
- Radiation Oncology
- Cancer Biology
Background:
- Perineural invasion (PNI) is a poor prognostic indicator in cancer, linked to increased recurrence.
- The precise mechanisms by which radiation therapy (RT) controls PNI are not fully understood.
Purpose of the Study:
- To investigate the mechanisms by which RT affects PNI.
- To explore RT's impact on both cancer cells and the nerve microenvironment in PNI models.
Main Methods:
- Utilized an in vitro co-culture system of dorsal root ganglia (DRG) and pancreatic cancer cells.
- Employed an in vivo murine sciatic nerve model to assess RT effects on PNI.
Main Results:
- DRG-secreted GDNF partially mediated cancer cell invasion.
- RT of DRG alone inhibited PNI, reducing GDNF secretion while preserving DRG viability.
- RT of cancer cells alone reduced PNI via decreased cancer cell viability.
- In vivo, RT of the sciatic nerve before cancer cell implantation decreased GDNF, PNI, and preserved nerve function.
Conclusions:
- RT can impair PNI through direct effects on cancer cells and by disrupting paracrine mechanisms.
- Modulating the nerve microenvironment with RT offers therapeutic potential for PNI in various cancers.
