Vitronectin as a molecular player of the tumor microenvironment in neuroblastoma

BMC Cancer

Adela Cañete¹  Inmaculada Noguera²  Rebeca Burgos-Panadero³  Rosa Noguera³  Samuel Navarro³ 

[1] 0000 0001 0360 9602, grid.84393.35, Pediatric Oncology Unit, University and Polytechnic Hospital La Fe, Valencia, Spain;0000 0001 2173 938X, grid.5338.d, Central Support Service for Experimental Research (SCSIE), University of Valencia, Valencia, Spain;0000 0001 2173 938X, grid.5338.d, Pathology Department, Medical School, University of Valencia-INCLIVA, Valencia, Spain;CIBERONC, Madrid, Spain;

关键词: Extracellular matrix;    Vitronectin;    Digital pathology;    Migration;    Neuroblastoma;   

DOI  :  10.1186/s12885-019-5693-2

来源: publisher

【 摘 要 】

BackgroundVitronectin is a multifunctional glycoprotein known in several human tumors for its adhesive role in processes such as cell growth, angiogenesis and metastasis. In this study, we examined vitronectin expression in neuroblastoma to investigate whether this molecule takes part in cell-cell or cell-extracellular matrix interactions that may confer mechanical properties to promote tumor aggressiveness.MethodsWe used immunohistochemistry and image analysis tools to characterize vitronectin expression and to test its prognostic value in 91 neuroblastoma patients. To better understand the effect of vitronectin, we studied its in vitro expression using commercial neuroblastoma cell lines and in vivo using intra-adrenal gland xenograft models by immunohistochemistry.ResultsDigital image analysis allowed us to associate vitronectin staining intensity and location discriminating between territorial vitronectin and interterritorial vitronectin expression patterns. High territorial vitronectin expression (strong staining associated with pericellular and intracellular location) was present in tumors from patients with metastatic undifferentiating neuroblastoma, that were MYCN amplified, 11q deleted or with segmental chromosomal profiles, in the high-risk stratification group and with high genetic instability. In vitro studies confirmed that vitronectin is expressed in tumor cells as small cytoplasmic dot drops. In vivo experiments revealed tumor cells with high and dense cytoplasmic vitronectin expression.ConclusionsThese findings highlight the relevance of vitronectin in neuroblastoma tumor biology and suggest its potential as a future therapeutic target in neuroblastoma.

【 授权许可】

CC BY