Inhibition of neuroblastoma-induced angiogenesis by fenretinide

Domenico Ribatti, Giulio Alessandri, Manuela Baronio, Lizzia Raffaghello, Emilio Cosimo, Danilo Marimpietri, Paolo Giuseppe Montaldo, Giuseppe De Falco, Arnaldo Caruso, Angelo Vacca, Mirco Ponzoni

Research output: Contribution to journalArticle

Abstract

Retinoids are a class of natural or synthetic compounds that participate in the control of cell proliferation, differentiation and fetal development. The synthetic retinoid fenretinide (HPR) inhibits carcinogenesis in various animal models. Retinoids have also been suggested to be effective inhibitors of angiogenesis. The effects of HPR on certain endothelial cell functions were investigated in vitro, and its effects on angiogenesis was studied in vivo, by using the chorioallantoic membrane (CAM) assay. HPR inhibited vascular endothelial growth factor- (VEGF-) and fibroblast growth factor-2- (FGF-2)-induced endothelial cell proliferation without affecting endothelial motility; moreover, HPR inhibited growth factor-induced angiogenesis in the CAM assay. Furthermore, a significant antiangiogenic potential of HPR has also been observed in neuroblastoma (NB) biopsy-induced angiogenesis in vivo. We previously demonstrated that supernatants derived from NB cell lines stimulated endothelial cell proliferation. In the present study, we found that this effect was abolished when NB cells were incubated in the presence of HPR. VEGF- and FGF-2-specific ELISA assays, performed on both NB cells derived from conditioned medium and cellular extracts, indicated no consistent effect of HPR on the level of these angiogenic cytokines. Moreover, RT-PCR analysis of VEGF and FGF-2 gene expression confirmed the above lack of effect. HPR was also able to significantly repress the spontaneous growth of endothelial cells, requiring at least 48-72 hr of treatment with HPR, followed by a progressive accumulation of cells in G1 at subsequent time points. Finally, immunohistochemistry experiments performed in the CAM assay demonstrated that endothelial staining of both VEGF receptor 2 and FGF-2 receptor-2 was reduced after implantation of HPR-loaded sponges, as compared to control CAMs. These data suggest that HPR exerts its antiangiogenic activity through both a direct effect on endothelial cell proliferative activity and an inhibitory effect on the responsivity of the endothelial cells to the proliferative stimuli mediated by angiogenic growth factors.

Original languageEnglish
Pages (from-to)314-321
Number of pages8
JournalInternational Journal of Cancer
Volume94
Issue number3
DOIs
Publication statusPublished - Nov 1 2001

Fingerprint

Fenretinide
Neuroblastoma
Endothelial Cells
Chorioallantoic Membrane
Retinoids
Fibroblast Growth Factor 2
Vascular Endothelial Growth Factor A
Cell Proliferation
Intercellular Signaling Peptides and Proteins
Receptor, Fibroblast Growth Factor, Type 2
Vascular Endothelial Growth Factor Receptor
Angiogenesis Inhibitors
Angiogenesis Inducing Agents
Porifera
Conditioned Culture Medium
Fetal Development
Cell Differentiation
Carcinogenesis
Animal Models
Enzyme-Linked Immunosorbent Assay

Keywords

  • Angiogenesis
  • Anti-angiogenesis
  • Fenretinide
  • Neuroblastoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Inhibition of neuroblastoma-induced angiogenesis by fenretinide. / Ribatti, Domenico; Alessandri, Giulio; Baronio, Manuela; Raffaghello, Lizzia; Cosimo, Emilio; Marimpietri, Danilo; Montaldo, Paolo Giuseppe; De Falco, Giuseppe; Caruso, Arnaldo; Vacca, Angelo; Ponzoni, Mirco.

In: International Journal of Cancer, Vol. 94, No. 3, 01.11.2001, p. 314-321.

Research output: Contribution to journalArticle

Ribatti, Domenico ; Alessandri, Giulio ; Baronio, Manuela ; Raffaghello, Lizzia ; Cosimo, Emilio ; Marimpietri, Danilo ; Montaldo, Paolo Giuseppe ; De Falco, Giuseppe ; Caruso, Arnaldo ; Vacca, Angelo ; Ponzoni, Mirco. / Inhibition of neuroblastoma-induced angiogenesis by fenretinide. In: International Journal of Cancer. 2001 ; Vol. 94, No. 3. pp. 314-321.
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AU - Cosimo, Emilio

AU - Marimpietri, Danilo

AU - Montaldo, Paolo Giuseppe

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