The role of Lutheran/basal cell adhesion molecule in human bladder carcinogenesis

Hong Yi Chang, Hsin Mei Chang, Tsung Jung Wu, Chang Yao Chaing, Tzong Shin Tzai, Hong Lin Cheng, Giri Raghavaraju, Nan Haw Chow, Hsiao Sheng Liu

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Abstract

Background: Lutheran/basal cell adhesion molecule (Lu/BCAM) is a membrane bound glycoprotein. This study was performed to investigate the role and downstream signaling pathway of Lu/BCAM in human bladder tumorigenesis. Methods: Five human bladder cancer (E6, RT4, TSGH8301, TCCSUP and J82), one stable mouse fibroblast cell line (NIH-Lu) expressing Lu/BCAM transgene and sixty human uroepithelial carcinoma specimens were analyzed by real-time PCR, immunohistochemistry (IHC), immunofluorescence (IFA) staining, Western blotting and promoter luciferase assay for Lu/BCAM, respectively. The tumorigenicity of Lu/BCAM was demonstrated by focus formation, colony-forming ability, tumour formation, cell adhesion and migration. Results: H-ras V12 was revealed to up-regulate Lu/BCAM at both transcriptional and translation levels. Lu/BCAM expression was detected on the membrane of primary human bladder cancer cells. Over-expression of Lu/BCAM in NIH-Lu stable cells increased focus number, colony formation and cell adhesion accompanied with F-actin rearrangement and decreased cell migration compared with parental NIH3T3 fibroblasts. In the presence of laminin ligand, Lu/BCAM overexpression further suppressed cell migration accompanied with increased cell adhesion. We further revealed that laminin-Lu/BCAM-induced cell adhesion and F-actin rearrangement were through increased Erk phosphorylation with an increase of RhoA and a decrease of Rac1 activity. Similarly, high Lu/BCAM expression was detected in the tumors of human renal pelvis, ureter and bladder, and was significantly associated with advanced tumor stage (p = 0.02). Patients with high Lu/BCAM expression showed a trend toward larger tumor size (p = 0.07) and lower disease-specific survival (p = 0.08), although not reaching statistical significance. Conclusion: This is the first report showing that Lu/BCAM, in the presence of its ligand laminin, is oncogenic in human urothelial cancers and may have potential as a novel therapeutic target.

Original languageEnglish
Article number61
JournalJournal of biomedical science
Volume24
Issue number1
DOIs
Publication statusPublished - 2017 Aug 26

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All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Pharmacology (medical)

Cite this

Chang, H. Y., Chang, H. M., Wu, T. J., Chaing, C. Y., Tzai, T. S., Cheng, H. L., Raghavaraju, G., Chow, N. H., & Liu, H. S. (2017). The role of Lutheran/basal cell adhesion molecule in human bladder carcinogenesis. Journal of biomedical science, 24(1), [61]. https://doi.org/10.1186/s12929-017-0360-x