Involvement of visinin-like protein-1 (VSNL-1) in regulating proliferative and invasive properties of neuroblastoma.
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.
Xie
Yi
Y
Department of Surgery, The University of Hong Kong, Hong Kong SAR, China.
Chan
Hiuman
H
Fan
Jianqing
J
Chen
Yongxiong
Y
Young
Joseph
J
Li
Wen
W
Miao
Xiaoping
X
Yuan
Zhengwei
Z
Wang
Huanmin
H
Tam
Paul K H
PK
Ren
Yi
Y
D001932:Brain Neoplasms / Q000473:pathology* / Q000601:surgery; D002455:Cell Division / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002999:Clone Cells; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000473:pathology*; D009447:Neuroblastoma / Q000473:pathology* / Q000601:surgery; D051596:Neurocalcin / Q000502:physiology*; D015398:Signal Transduction
D051596:Neurocalcin; C496688:VSNL1 protein, human