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Multidrug resistance transporter profile reveals MDR3 as a marker for
stratification of blastemal Wilms tumour patients
#MMPMID28061436
Hontecillas-Prieto L
; Garcia-Dominguez DJ
; Vaca DP
; Garcia-Mejias R
; Marcilla D
; Ramirez-Villar GL
; Saez C
; de Álava E
Oncotarget
2017[Feb]; 8
(7
): 11173-11186
PMID28061436
show ga
Wilms tumour (WT) is the most common renal tumour in children. Most WT patients
respond to chemotherapy, but subsets of tumours develop resistance to
chemotherapeutic agents, which is a major obstacle in their successful treatment.
Multidrug resistance transporters play a crucial role in the development of
resistance in cancer due to the efflux of anticancer agents out of cells. The aim
of this study was to explore several human multidrug resistance transporters in
46 WT and 40 non-neoplastic control tissues (normal kidney) from patients
selected after chemotherapy treatment SIOP 93-01, SIOP 2001. Our data showed that
the majority of the studied multidrug resistance transporters were downregulated
or unchanged between tumours and control tissues. However, BCRP1, MDR3 and MRP1
were upregulated in tumours versus control tissues. MDR3 and MRP1 overexpression
correlated with high-risk tumours (SIOP classification) (p = 0.0022 and p <
0.0001, respectively) and the time of disease-free survival was significantly
shorter in patients with high transcript levels of MDR3 (p = 0.0359). MDR3 and
MRP1 play a role in drug resistance in WT treatment, probably by alteration of an
unspecific drug excretion system. Besides, within the blastemal subtype, we
observed patients with low MDR3 expression were significantly associated with a
better outcome than patients with high MDR3 expression. We could define two types
of blastemal WT associated with different disease outcomes, enabling the
stratification of blastemal WT patients based on the expression levels of the
multidrug resistance transporter MDR3.
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