Journal Article

Involvement of visinin-like protein-1 (VSNL-1) in regulating proliferative and invasive properties of neuroblastoma

Yi Xie, Hiuman Chan, Jianqing Fan, Yongxiong Chen, Joseph Young, Wen Li, Xiaoping Miao, Zhengwei Yuan, Huanmin Wang, Paul K.H. Tam and Yi Ren

in Carcinogenesis

Volume 28, issue 10, pages 2122-2130
Published in print October 2007 | ISSN: 0143-3334
Published online July 2007 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgm147
Involvement of visinin-like protein-1 (VSNL-1) in regulating proliferative and invasive properties of neuroblastoma

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Tumor growth and metastasis require that tumor cells must have either the potential to shift genetically or epigenetically between proliferative and invasive phenotypes or both phenotypes simultaneously. In the present study, we demonstrated that neuroblastoma growth and invasion were distinct processes that were carried out by proliferative and invasive phenotypes of tumor cells, respectively. Two subpopulations from human neuroblastoma cell line were isolated: highly invasive (HI) cells and low-invasive (LI) cells. HI and LI cells had different proliferative rate and metastatic ability in vitro and in vivo. In addition, they had distinct activated signal pathways and sensitivities to chemotherapy drugs. Affymetrix microarray and quantitative reverse transcriptase–polymerase chain reaction revealed that visinin-like protein-1 (VSNL-1) mRNA in HI cells was significantly higher than that in LI cells. We also observed that VSNL-1 was over-expressed in tumor specimens from patients with distant organ metastases compared with those without metastases. Furthermore, the invasive and proliferative phenotypes of neuroblastoma cells could be exchanged by regulation of VSNL-1 expression in vitro and in vivo. Up-regulation of VSNL-1 potentiated the anoikis-resistant ability of neuroblastoma cell. The expression of anoikis inhibitor TrkB, intracellular adhesion molecule 1, major histocompatibility complex class I, CD44 and CD44v6 was associated with VSNL-1 level. These results suggested that distinct roles of proliferative and invasive phenotypes contributed to neuroblastoma progression and strongly demonstrated that VSNL-1 played a very important role in neuroblastoma metastasis.

Journal Article.  6077 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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