Role of L1 Cell Adhesion Molecule in Adhesion-Mediated Proliferation and Chemoresistance of Retinoblastoma

Abstract

 

Purpose

 

Although retinoblastoma is the most common intraocular malignancy in children, there have been limited studies on which drives distinct proliferation patterns and responses to chemotherapy in retinoblastoma. In this study, we investigated the role of L1 cell adhesion molecule (L1CAM) in adhesion-mediated tumor behavior and chemoresistance of retinoblastoma.

 

Methods

 

We evaluated the expression of L1CAM in retinoblastoma tissues from 30 patients by immunohistochemistry and in cell lines by Western blotting. To study the role of L1CAM in proliferation and chemoresistance in retinoblastoma, we utilized two retinoblastoma cell lines, Y79 and SNUOT-Rb1, with knockdown and overexpression of L1CAM, respectively. Then, the effects of L1CAM expression on proliferation, cell-cell adhesion, and chemoresistance of retinoblastoma cells were investigated. We injected naïve and stable cell lines into the vitreous cavity of BALB/c nude mice (n = 6) to demonstrate the relation between L1CAM and in vivo tumor formation.

 

Results

 

We observed varying degrees of L1CAM positivity in 86.6% (26/30) of retinoblastoma tissues. Interestingly, there was an inverse relation between the degree of Flexner-Wintersteiner rosette formation and that of L1CAM positivity. In vitro studies using stable cell lines demonstrated that L1CAM was associated with cell-cell adhesion and further adhesion-mediated proliferation of retinoblastoma cells. In addition, L1CAM was related with chemoresistance to carboplatin, one of the most widely utilized drug in the treatment of retinoblastoma. In line with in vitro results, in vivo tumor formation in rodent eyes was also more prominent with cell lines with higher expression of L1CAM.

 

Conclusions

 

Our results show that L1CAM is expressed in retinoblastoma and plays an important role in adhesion-mediated proliferation and chemoresistance of tumor cells. We suggest that profound understanding of the roles of L1CAM may open up another therapeutic approach against retinoblastoma.  

 

Representative photographs of L1CAM expression in retinoblastoma tissues. Scale bar, 20 μm.

 

 

Expression of L1CAM protein among different cells. HRMEC, human retinal microvascular endothelial cells; Rb1, SNUOT-Rb1 cells.