title: Hyperglycemic tumor microenvironment induces perineural invasion in pancreatic cancer.
abstract: Glucose intolerance and frank diabetes mellitus (DM) can increase the risk of cancer death for pancreatic cancer (PanCa). However, the mechanism by which these factors influence cancer deaths is not clear. In this study, we established a model system to mimic the pancreatic tumor microenvironment in patients with DM to examine the biological behavior of PanCa cells and nerves in cell culture and in animals. Our in vitro studies demonstrated that hyperglycemia promoted the proliferation and invasion of PanCa cell lines and upregulated the expression of nerve growth factor in these cells. Also, the migration of Schwann cells (SCs) was inhibited by hyperglycemia and neurites exerted pathological regeneration. Furthermore, the interaction between the PanCa cells and nerves was enhanced in the tumor microenvironment. We further showed that hyperglycemia promoted the perineural invasion (PNI) of PanCa in vivo. These data suggest that DM worsens the prognosis of PanCa because of aggravated PNI. Thus, our study illustrates a novel mechanism by which hyperglycemia decreases survival in patients with PanCa.
authors.affiliation: a Department of Hepatobiliary Surgery ; First Affiliated Hospital of Medical College; Xi'an Jiaotong University ; Xi'an , China.
authors.forename: Junhui
authors.initials: J
authors.lastname: Li
authors.forename: Jiguang
authors.initials: J
authors.lastname: Ma
authors.forename: Liang
authors.initials: L
authors.lastname: Han
authors.forename: Qinhong
authors.initials: Q
authors.lastname: Xu
authors.forename: Jianjun
authors.initials: J
authors.lastname: Lei
authors.forename: Wanxing
authors.initials: W
authors.lastname: Duan
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Fengfei
authors.initials: F
authors.lastname: Wang
authors.forename: Erxi
authors.initials: E
authors.lastname: Wu
authors.forename: Qingyong
authors.initials: Q
authors.lastname: Ma
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Huo
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D005727:Ganglia, Spinal / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D016501:Neurites / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D010525:Peripheral Nerves / Q000473:pathology*; D010524:Peripheral Nervous System Neoplasms / Q000378:metabolism / Q000473:pathology; D051381:Rats; D020800:Receptor, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D020917:Receptor, trkA / Q000235:genetics / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism; D012584:Sciatic Nerve / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D059016:Tumor Microenvironment
chemical_list: D020800:Receptor, Nerve Growth Factor; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D005947:Glucose
keywords: DM, diabetes mellitus; DRGs, dorsal root ganglions; NGF; PNI, perineural invasion; PanCa, pancreatic cancer; SCs, Schwann cells.; hyperglycemia; metastasis; pancreatic cancer; perineural invasion