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Pancreatic Neoplasms: HELP
Articles by Shizhi He
Based on 2 articles published since 2010
(Why 2 articles?)
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Between 2010 and 2020, Shizhi He wrote the following 2 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article Inflammatory Monocytes Promote Perineural Invasion via CCL2-Mediated Recruitment and Cathepsin B Expression. 2017

Bakst, Richard L / Xiong, Huizhong / Chen, Chun-Hao / Deborde, Sylvie / Lyubchik, Anna / Zhou, Yi / He, Shizhi / McNamara, William / Lee, Sei-Young / Olson, Oakley C / Leiner, Ingrid M / Marcadis, Andrea R / Keith, James W / Al-Ahmadie, Hikmat A / Katabi, Nora / Gil, Ziv / Vakiani, Efsevia / Joyce, Johanna A / Pamer, Eric / Wong, Richard J. ·Department of Radiation Oncology, Mount Sinai School of Medicine, New York, New York. · Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, New York. · Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York. · Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Otolaryngology, Rambam Healthcare Campus, The Technion-Israel Institute of Technology, Haifa, Israel. · Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland. · Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York. wongr@mskcc.org. ·Cancer Res · Pubmed #28951461.

ABSTRACT: Perineural invasion (PNI) is an ominous event strongly linked to poor clinical outcome. Cells residing within peripheral nerves collaborate with cancer cells to enable PNI, but the contributing conditions within the tumor microenvironment are not well understood. Here, we show that CCR2-expressing inflammatory monocytes (IM) are preferentially recruited to sites of PNI, where they differentiate into macrophages and potentiate nerve invasion through a cathepsin B-mediated process. A series of adoptive transfer experiments with genetically engineered donors and recipients demonstrated that IM recruitment to nerves was driven by CCL2 released from Schwann cells at the site of PNI, but not CCL7, an alternate ligand for CCR2. Interruption of either CCL2-CCR2 signaling or cathepsin B function significantly impaired PNI

2 Article GFRα1 released by nerves enhances cancer cell perineural invasion through GDNF-RET signaling. 2014

He, Shuangba / Chen, Chun-Hao / Chernichenko, Natalya / He, Shizhi / Bakst, Richard L / Barajas, Fernando / Deborde, Sylvie / Allen, Peter J / Vakiani, Efsevia / Yu, Zhenkun / Wong, Richard J. ·Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021;Department of Otolaryngology, Anhui Provincial Hospital, Anhui Medical University, Anhui 230001, China; · Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021; · Department of Radiation Oncology, Mount Sinai Hospital, New York, NY 10029; · Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 20021; and. · Department of Otolaryngology, Nanjing Tongren Hospital, Southeast University, Nanjing 211102, China. · Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021; wongr@mskcc.org. ·Proc Natl Acad Sci U S A · Pubmed #24778213.

ABSTRACT: The ability of cancer cells to invade along nerves is associated with aggressive disease and diminished patient survival rates. Perineural invasion (PNI) may be mediated by nerve secretion of glial cell line-derived neurotrophic factor (GDNF) attracting cancer cell migration through activation of cell surface Ret proto-oncogene (RET) receptors. GDNF family receptor (GFR)α1 acts as coreceptor with RET, with both required for response to GDNF. We demonstrate that GFRα1 released by nerves enhances PNI, even in the absence of cancer cell GFRα1 expression. Cancer cell migration toward GDNF, RET phosphorylation, and MAPK pathway activity are increased with exposure to soluble GFRα1 in a dose-dependent fashion. Dorsal root ganglia (DRG) release soluble GFRα1, which potentiates RET activation and cancer cell migration. In vitro DRG coculture assays of PNI show diminished PNI with DRG from GFRα1(+/-) mice compared with GFRα1(+/+) mice. An in vivo murine model of PNI demonstrates that cancer cells lacking GFRα1 maintain an ability to invade nerves and impair nerve function, whereas those lacking RET lose this ability. A tissue microarray of human pancreatic ductal adenocarcinomas demonstrates wide variance of cancer cell GFRα1 expression, suggesting an alternate source of GFRα1 in PNI. These findings collectively demonstrate that GFRα1 released by nerves enhances PNI through GDNF-RET signaling and that GFRα1 expression by cancer cells enhances but is not required for PNI. These results advance a mechanistic understanding of PNI and implicate the nerve itself as a key facilitator of this adverse cancer cell behavior.