Bin1 is linked to metastatic potential and chemosensitivity in neuroblastoma.
BACKGROUND
Neuroblastoma (NB) is the most common extracranial solid tumor in children. At the time of diagnosis, the tumor has metastasized in as many as 7 of 10 cases, and survival in high-risk patients remains poor. Accurate classification of high-risk patients is very important since this determines treatment plan, and although a consensus risk classification system has been established for NB, it contains few specific molecular markers that account for aggressive nature and metastatic potential of the tumor. Bin1 expression is reduced in breast, NB, and other cancer types and the reduction correlates with high-risk clinical features. Here we hypothesize that Bin1 has an inhibitory role in metastasis, and therefore decrease in its expression may be a marker of high-risk NB.


METHODS
Initially, breast cancer and NB cell lines derived from metastasis were examined for Bin1 expression. Then, a stable Bin1-overexpressing NB cell line was created and evaluated for in vitro metastatic behaviors using anoikis, invasion, and migration assays, and chemoresponsiveness using MTT assay.


RESULTS
Reduced Bin1 was detected in all cancer cell lines examined, and forced Bin1 overexpression increased NB cell anoikis and enhanced the cell killing by doxorubicin. However, Bin1 overexpression did not significantly affect cell invasion, motility, or proliferation.


CONCLUSIONS
Bin1 appears to function as a metastasis suppressor and chemosensitizer in NB, and resistance to anoikis may be an important metastatic mechanism. Thus, Bin1 expression status could serve as a marker for metastatic potential and chemosensitivity thereby allowing for more accurate classifications of high-risk NB patients.
Department of Surgery, Section of Pediatric Surgery, Riley Children's Hospital, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. xzhong@iupui.edu
Xiaoling
X
Zhong
Derek J
DJ
Hoelz
Hari R
HR
Kumar
John A
JA
Sandoval
Frederick J
FJ
Rescorla
Robert J
RJ
Hickey
Linda H
LH
Malkas
D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000502:physiology*; D023102:Anoikis / Q000187:drug effects; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology*; D009687:Nuclear Proteins / Q000032:analysis / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; C101410:BIN1 protein, human; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D004317:Doxorubicin