Increased TGFβ type II receptor expression suppresses the malignant phenotype and induces differentiation of human neuroblastoma cells

Alessandra Turco, Susanna Scarpa, Anna Coppa, Gianluca Baccheschi, Camilla Palumbo, Carlo Leonetti, Gabriella Zupi, Giulia Colletta

Research output: Contribution to journalArticle

Abstract

TGFβ can modulate neuroblastoma (NB) cell proliferation and differentiation in vitro. In this study we used a NB cell line (LAN-5) which has been shown to partially respond to TGFβ and to present high levels of TGFβ receptor type I and low levels of receptor type II (TβRII) on the cell surface. To evaluate the role of TβRII in mediating TGFβ effects, LAN-5 cells were transfected with an expression vector containing the human full- length TβRII cDNA or with the empty vector pcDNA3. Compared to control CLV3 cells (transfected with empty plasmid) and parental LAN-5 cells, isolated neomycin-resistant clones (CL1 and CL3) expressed higher levels of TβRII, had reduced cell growth rate in vitro, and were unable to form tumors in vivo. Furthermore, isolated clones modified their morphology, assuming a terminally differentiated neuronal phenotype. Immunocytochemical staining demonstrated a basal increased expression of neural-specific markers, such as axonal growth-associated protein (GAP43) and neurofilaments (NF200). TGFβ treatment further increased the synthesis of NF200 and GAP43 in the transfected clones as revealed by Western blot analysis. These data indicate that TβRII overexpression potentiates the TGFβ signal transduction pathway, reverting NB cell neoplastic phenotype with the reduction of proliferation rate and the induction of terminal maturation. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)77-85
Number of pages9
JournalExperimental Cell Research
Volume255
Issue number1
DOIs
Publication statusPublished - Feb 25 2000

Keywords

  • Neuroblastoma cells
  • Neuronal markers
  • TβRII
  • TGFβ

ASJC Scopus subject areas

  • Cell Biology

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