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


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.

SUBMITTER: Chang HY 

PROVIDER: S-EPMC6389174 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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

Chang Hong-Yi HY   Chang Hsin-Mei HM   Wu Tsung-Jung TJ   Chaing Chang-Yao CY   Tzai Tzong-Shin TS   Cheng Hong-Lin HL   Raghavaraju Giri G   Chow Nan-Haw NH   Liu Hsiao-Sheng HS  

Journal of biomedical science 20170826 1


<h4>Background</h4>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.<h4>Methods</h4>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), immunofluo  ...[more]

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