title: LRRN4 and UPK3B are markers of primary mesothelial cells.
abstract: BACKGROUND
  Mesothelioma is a highly malignant tumor that is primarily caused by occupational or environmental exposure to asbestos fibers. Despite worldwide restrictions on asbestos usage, further cases are expected as diagnosis is typically 20-40 years after exposure. Once diagnosed there is a very poor prognosis with a median survival rate of 9 months. Considering this the development of early pre clinical diagnostic markers may help improve clinical outcomes.
  
  
  METHODS
  Microarray expression arrays on mesothelium and other tissues dissected from mice were used to identify candidate mesothelial lineage markers. Candidates were further tested by qRTPCR and in-situ hybridization across a mouse tissue panel. Two candidate biomarkers with the potential for secretion, uroplakin 3B (UPK3B), and leucine rich repeat neuronal 4 (LRRN4) and one commercialized mesothelioma marker, mesothelin (MSLN) were then chosen for validation across a panel of normal human primary cells, 16 established mesothelioma cell lines, 10 lung cancer lines, and a further set of 8 unrelated cancer cell lines.
  
  
  CONCLUSIONS
  Within the primary cell panel, LRRN4 was only detected in primary mesothelial cells, but MSLN and UPK3B were also detected in other cell types. MSLN was detected in bronchial epithelial cells and alveolar epithelial cells and UPK3B was detected in retinal pigment epithelial cells and urothelial cells. Testing the cell line panel, MSLN was detected in 15 of the 16 mesothelioma cells lines, whereas LRRN4 was only detected in 8 and UPK3B in 6. Interestingly MSLN levels appear to be upregulated in the mesothelioma lines compared to the primary mesothelial cells, while LRRN4 and UPK3B, are either lost or down-regulated. Despite the higher fraction of mesothelioma lines positive for MSLN, it was also detected at high levels in 2 lung cancer lines and 3 other unrelated cancer lines derived from papillotubular adenocarcinoma, signet ring carcinoma and transitional cell carcinoma.
authors: OMICs Science Center, RIKEN Yokohama Institute, Yokohama, Kanagawa, Japan.
authors: Mutsumi
authors: M
authors: Kanamori-Katayama
authors: Ai
authors: A
authors: Kaiho
authors: Yuri
authors: Y
authors: Ishizu
authors: Yuko
authors: Y
authors: Okamura-Oho
authors: Okio
authors: O
authors: Hino
authors: Masaaki
authors: M
authors: Abe
authors: Takumi
authors: T
authors: Kishimoto
authors: Hisahiko
authors: H
authors: Sekihara
authors: Yukio
authors: Y
authors: Nakamura
authors: Harukazu
authors: H
authors: Suzuki
authors: Alistair R R
authors: AR
authors: Forrest
authors: Yoshihide
authors: Y
authors: Hayashizaki
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D019070:Cell Lineage; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D004848:Epithelium / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008168:Lung / Q000166:cytology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D000090204:Mesothelin; D008654:Mesothelioma / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060171:Uroplakin III / Q000235:genetics / Q000378:metabolism
chemical_list: D000912:Antibodies, Neoplasm; D015415:Biomarkers; C569562:LRRN4 protein, human; C000715527:MSLN protein, human; D008565:Membrane Proteins; C000715528:Msln protein, mouse; D009419:Nerve Tissue Proteins; C554662:UPK3B protein, human; D060171:Uroplakin III; D000090204:Mesothelin