Title: Gene expression changes in melanoma metastases in response to high-dose chemotherapy during isolated limb perfusion
Authors: Wouters, Jasper ×
Stas, Marguerite
Govaere, Olivier
Van den Eynde, Kathleen
Vankelecom, Hugo
van den Oord, Joost J #
Issue Date: Jul-2012
Publisher: Wiley-Blackwell Publishing, Inc
Series Title: Pigment Cell & Melanoma Research vol:25 issue:4 pages:454-465
Abstract: Despite recent advances in melanoma therapy, disseminated melanoma still lacks effective treatment, and recurrence of the tumor frequently occurs, even after high-dose chemotherapy. The mechanisms responsible for this chemoresistance or for the formation of new relapses remain poorly understood. Using a human 'model', in which the isolated limb is perfused with high doses of the chemotherapeutic melphalan (ILP), we identified a five-gene set (ATF3, CYR61, IER5, IL6, and PTGS2) of stress-induced genes that was consistently upregulated after ILP in all in-transit metastatic melanoma samples as well as in three melphalan-treated melanoma cell lines. Early post-ILP relapses retained these elevated expressions, whereas the expression of these genes returned to their original levels in late post-ILP recurrences. In addition, we identified upregulation of these genes in the A375 cell line's side population (SP) and melanospheres, established methods to enrich for candidate cancer stem cells (CSCs), which are considered chemoresistant and tumorigenic, and thus proposed to be responsible for tumor relapse. Our data identify an immediate and short-term upregulation of early stress-responsive genes that are potentially linked to chemoresistance and CSCs.
ISSN: 1755-1471
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Translational Cell & Tissue Research
Surgical Oncology
Embryo and Stemcells (-)
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science