title: Establishment of perineural invasion models and analysis of gene expression revealed an invariant chain (CD74) as a possible molecule involved in perineural invasion in pancreatic cancer.
abstract: OBJECTIVE
  Perineural invasion causes frequent local recurrence even after resection and a poor prognosis for pancreatic cancer. We established perineural invasion models and analyzed the molecular mechanism of perineural invasion in pancreatic cancer.
  
  
  METHODS
  Seven pancreatic cancer cell lines with or without human peripheral nerves were s.c. implanted in nonobese diabetes/severe combined immunodeficient mice. We compared expression profiles among high and low perineural invasion cell lines by using an oligonucleotide microarray. We examined up-regulation of the invariant chain (CD74) in high perineural invasion cell lines in mRNA and protein levels and surgical cases immunohistochemically.
  
  
  RESULTS
  Four of seven pancreatic cancer cell lines (CaPan1, CaPan2, CFPAC, and MPanc96) showed perineural invasion to s.c. transplanted human peripheral nerves. Moreover, CaPan1 and CaPan2 (high perineural invasion group) also resulted in a high frequency of perineural invasion to mouse s.c. peripheral nerves, whereas three pancreatic cancer cell lines HPAFII, AsPC1, and Panc1 (low perineural invasion group) did not show perineural invasion to either human or mouse nerves. We identified 37 up-regulated genes and 12 down-regulated genes in the high perineural invasion group compared with the low perineural invasion group. Among them, CD74 was up-regulated in the high perineural invasion group in mRNA and protein levels. Furthermore, immunohistochemical expression of CD74 in clinical cases revealed its significant overexpression in pancreatic cancer with perineural invasion (P < 0.008).
  
  
  CONCLUSIONS
  This is the first report of perineural invasion models using human pancreatic cancer cell lines. In combination with gene expression profiling, it was indicated that CD74 could be a candidate molecule involved in perineural invasion. These models provide new approaches for study of perineural invasion in pancreatic cancer.
authors.affiliation: Departments of Pathology and Surgery, School of Medicine, Keio University, USA.
authors.forename: Norimasa
authors.initials: N
authors.lastname: Koide
authors.forename: Taketo
authors.initials: T
authors.lastname: Yamada
authors.forename: Rie
authors.initials: R
authors.lastname: Shibata
authors.forename: Taisuke
authors.initials: T
authors.lastname: Mori
authors.forename: Mariko
authors.initials: M
authors.lastname: Fukuma
authors.forename: Ken
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Koichi
authors.initials: K
authors.lastname: Aiura
authors.forename: Motohide
authors.initials: M
authors.lastname: Shimazu
authors.forename: Setsuo
authors.initials: S
authors.lastname: Hirohashi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nimura
authors.forename: Michiie
authors.initials: M
authors.lastname: Sakamoto
mesh_terms: D000368:Aged; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis / Q000235:genetics*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010525:Peripheral Nerves / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; C045084:invariant chain