Bin1 is linked to metastatic potential and chemosensitivity in neuroblastoma

Xiaoling Zhong, Derek J. Hoelz, Hari R. Kumar, John A. Sandoval, Frederick J. Rescorla, Robert J. Hickey, Linda H. Malkas

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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. Procedure. 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.

Original languageEnglish (US)
Pages (from-to)332-337
Number of pages6
JournalPediatric Blood and Cancer
Volume53
Issue number3
DOIs
StatePublished - Sep 1 2009

Fingerprint

Neuroblastoma
Anoikis
Neoplasms
Neoplasm Metastasis
Cell Line
Doxorubicin
Cell Movement
Breast
Cell Proliferation
Breast Neoplasms
Survival

Keywords

  • Anoikis
  • Bin1
  • Chemotherapeutic agent
  • Marker
  • Metastasis
  • Neuroblastoma

ASJC Scopus subject areas

  • Oncology
  • Pediatrics, Perinatology, and Child Health
  • Hematology

Cite this

Zhong, X., Hoelz, D. J., Kumar, H. R., Sandoval, J. A., Rescorla, F. J., Hickey, R. J., & Malkas, L. H. (2009). Bin1 is linked to metastatic potential and chemosensitivity in neuroblastoma. Pediatric Blood and Cancer, 53(3), 332-337. https://doi.org/10.1002/pbc.22068

Bin1 is linked to metastatic potential and chemosensitivity in neuroblastoma. / Zhong, Xiaoling; Hoelz, Derek J.; Kumar, Hari R.; Sandoval, John A.; Rescorla, Frederick J.; Hickey, Robert J.; Malkas, Linda H.

In: Pediatric Blood and Cancer, Vol. 53, No. 3, 01.09.2009, p. 332-337.

Research output: Contribution to journalArticle

Zhong, X, Hoelz, DJ, Kumar, HR, Sandoval, JA, Rescorla, FJ, Hickey, RJ & Malkas, LH 2009, 'Bin1 is linked to metastatic potential and chemosensitivity in neuroblastoma', Pediatric Blood and Cancer, vol. 53, no. 3, pp. 332-337. https://doi.org/10.1002/pbc.22068
Zhong, Xiaoling ; Hoelz, Derek J. ; Kumar, Hari R. ; Sandoval, John A. ; Rescorla, Frederick J. ; Hickey, Robert J. ; Malkas, Linda H. / Bin1 is linked to metastatic potential and chemosensitivity in neuroblastoma. In: Pediatric Blood and Cancer. 2009 ; Vol. 53, No. 3. pp. 332-337.
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abstract = "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. Procedure. 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.",
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AB - 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. Procedure. 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.

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