title: Characterization of tumorigenic cell lines from the recurrence and lymph node metastasis of a human salivary mucoepidermoid carcinoma.
abstract: The long-term outcome of patients with mucoepidermoid carcinoma is poor. Limited availability of cell lines and lack of xenograft models is considered a major barrier to improved mechanistic understanding of this disease and development of effective therapies.
  
  
  OBJECTIVE
  To generate and characterize human mucoepidermoid carcinoma cell lines and xenograft models suitable for mechanistic and translational studies.
  
  
  METHODS
  Five human mucoepidermoid carcinoma specimens were available for generation of cell lines. Cell line tumorigenic potential was assessed by transplantation and serial in vivo passaging in immunodeficient mice, and cell line authenticity verified by short tandem repeat (STR) profiling.
  
  
  RESULTS
  A unique pair of mucoepidermoid carcinoma cell lines was established from a local recurrence (UM-HMC-3A) and from the metastatic lymph node (UM-HMC-3B) of the same patient, 4 years after surgical removal of the primary tumor. These cell lines retained epithelial-like morphology through 100 passages in vitro, contain the Crtc1-Maml2 fusion oncogene (characteristic of mucoepidermoid carcinomas), and express the prototypic target of this fusion (NR4A2). Both cell lines generated xenograft tumors when transplanted into immunodeficient mice. Notably, the xenografts exhibited histological features and Periodic Acid Schiff (PAS) staining patterns that closely resembled those found in human tumors. STR profiling confirmed the origin and authenticity of these cell lines.
  
  
  CONCLUSIONS
  These data demonstrate the generation and characterization of a pair of tumorigenic salivary mucoepidermoid carcinoma cell lines representative of recurrence and lymph node metastasis. Such models are useful for mechanistic and translational studies that might contribute to the discovery of new therapies for mucoepidermoid carcinoma.
authors.affiliation: Department of Restorative Sciences, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA.
authors.forename: Kristy A
authors.initials: KA
authors.lastname: Warner
authors.forename: April
authors.initials: A
authors.lastname: Adams
authors.forename: Lisiane
authors.initials: L
authors.lastname: Bernardi
authors.forename: Carolina
authors.initials: C
authors.lastname: Nor
authors.forename: Kelsey A
authors.initials: KA
authors.lastname: Finkel
authors.forename: Zhaocheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Scott A
authors.initials: SA
authors.lastname: McLean
authors.forename: Joseph
authors.initials: J
authors.lastname: Helman
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Wolf
authors.forename: Vasu
authors.initials: V
authors.lastname: Divi
authors.forename: Lurdes
authors.initials: L
authors.lastname: Queimado
authors.forename: Frederic J
authors.initials: FJ
authors.lastname: Kaye
authors.forename: Rogerio M
authors.initials: RM
authors.lastname: Castilho
authors.forename: Jacques E
authors.initials: JE
authors.lastname: Nör
mesh_terms: D000368:Aged; D000818:Animals; D018277:Carcinoma, Mucoepidermoid / Q000235:genetics* / Q000556:secondary; D045744:Cell Line, Tumor / Q000473:pathology*; D005260:Female; D006801:Humans; D008198:Lymph Nodes; D008207:Lymphatic Metastasis / Q000235:genetics*; D008297:Male; D051379:Mice; D018895:Microsatellite Repeats; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D009374:Neoplasms, Experimental / Q000235:genetics; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C539882:NR4A2 protein, human; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D015514:Oncogene Proteins, Fusion
keywords: Crtc1–Maml2; Metastasis; Mouse models; Oral cancer; Salivary gland cancer; Tumor recurrence; Xenograft
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