Abstract
ABSTRACT: Neuroblastoma cells in response to retinoic acid (RA) exhibit differentiation. RA, which can promote tumor cell differentiation, has also been shown to regulate tumor-infiltrating leukocytes. In an attempt to explore the relationship between RA-induced neuroblastoma cell differentiation and leukocyte chemotaxis, we investigated expression of IL-1β, IL-8, granulocyte-macrophage colony stimulating factor, and tumor necrosis factor-α in the un-differentiated and RA-induced differentiated neuroblastoma cells. Using SK-N-SH neuroblastoma cells, we found that RA induced differentiation of SK-N-SH cells as demonstrated by down-regulation of N-myc gene expression, cell-cycle arrest in G1 phase, and phenotypic change. Neither RA-treated nor untreated neuroblastoma cells expressed IL-1β, granulocyte-macrophage colony stimulating factor, or tumor necrosis factor-α mRNA. RA-treated but not untreated SK-N-SH cells expressed IL-8 mRNA in a time- and dose-dependent fashion. As determined by ELISA, IL-8 levels were detectable in the culture supernatants from RA-treated, but not untreated, neuroblastoma cells (2.65 ± 0.43 versus 0.05 ± 0.04 ng/mL). Using neutrophil and lymphocyte chemotactic assays, we found that RA-treated but not untreated culture supernatants of neuroblastoma cells promoted neutrophil and lymphocyte chemotaxis. The RA enhancement of neuroblastoma cell-mediated leukocyte chemotaxis was significantly blocked by anti-IL-8 neutralizing antibodies. These results suggest that RA-induced neuroblastoma cell differentiation is associated with production of functional IL-8, which may be involved in the leukocyte infiltration and activation resulting in tumor regression.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Yang, K., Cheng, SN., Nia-Cheng, W. et al. Induction of Interleukin-8 Expression in Neuroblastoma Cells by Retinoic Acid: Implication of Leukocyte Chemotaxis and Activation. Pediatr Res 34, 720–724 (1993). https://doi.org/10.1203/00006450-199312000-00005
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1203/00006450-199312000-00005
This article is cited by
-
Targeting the myeloid microenvironment in neuroblastoma
Journal of Experimental & Clinical Cancer Research (2023)