radiation impairs perineural invasion by modulating the nerve microenvironment通过调节神经微环境辐射会损害神经周的入侵.pdfVIP

Radiation Impairs Perineural Invasion by Modulating the Nerve Microenvironment 1 1 2 2 2 2 Richard L. Bakst , Nancy Lee , Shuangba He , Natalya Chernichenko , Chun-Hao Chen , Gary Linkov , H. 3 3,4 5 2 Carl Le , Jason Koutcher , Efsevia Vakiani , Richard J. Wong * 1 Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America, 2 Department of Surgery, Memorial Sloan- Kettering Cancer Center, New York, New York, United States of America, 3 Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America, 4 Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America, 5 Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America Abstract Purpose: Perineural invasion (PNI) by cancer cells is an ominous clinical event that is associated with increased local recurrence and poor prognosis. Although radiation therapy (RT) may be delivered along the course of an invaded nerve, the mechanisms through which radiation may potentially control PNI remain undefined. Experimental Design: An in vitro co-culture system of dorsal root ganglia (DRG) and pancreatic cancer cells was used as a model of PNI. An in vivo murine sciatic nerve model was used to study how RT to nerve or cancer affects nerve invasion by cancer. Results: Cancer cell invasion of the DRG was partially dependent on DRG secretion of glial-derived neurotrophic factor (GDNF). A single 4 Gy dose of radiation to the DRG alone, cultured with non-radiated cancer ce