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Reduced expression of the murine HLA-G homolog Qa-2 is associated with
malignancy, epithelial-mesenchymal transition and stemness in breast cancer
cells
#MMPMID28740236
da Silva IL
; Montero-Montero L
; Martín-Villar E
; Martin-Pérez J
; Sainz B
; Renart J
; Toscano Simões R
; Soares Veloso É
; Salviano Teixeira C
; de Oliveira MC
; Ferreira E
; Quintanilla M
Sci Rep
2017[Jul]; 7
(1
): 6276
PMID28740236
show ga
Qa-2 is believed to mediate a protective immune response against cancer; however,
little is known about the role of Qa-2 in tumorigenesis. Here, we used 4T1 breast
cancer cells to study the involvement of Qa-2 in tumor progression in a syngeneic
host. Qa-2 expression was reduced during in vivo tumor growth and in cell lines
derived from 4T1-induced tumors. Tumor-derived cells elicited an
epithelial-mesenchymal transition associated with upregulation of Zeb1 and
Twist1/2 and enhanced tumor initiating and invasive capacities. Furthermore,
these cells showed increased stem characteristics, as demonstrated by
upregulation of Hes1, Sox2 and Oct3/4, and enrichment of
CD44(high)/CD24(median/low) cells. Remarkably, Qa-2 cell-surface expression was
excluded from the CD44(high)/CD24(median/low) subpopulation. Tumor-derived cells
showed increased Src activity, and treatment of these cells with the Src kinase
inhibitor PP2 enhanced Qa-2 but reduced Sox2 and CD44(high)/CD24(median/low)
expression levels, suggesting that Src signaling, while positively associated
with stemness, negatively regulates Qa-2 expression in breast cancer. Finally,
overexpression of the Qa-2 family member Q7 on the cell surface slowed down in
vivo tumor growth and reduced the metastatic potential of 4T1 cells. These
results suggest an anti-malignant role for Qa-2 in breast cancer development,
which appears to be absent from cancer stem cells.
|*Epithelial-Mesenchymal Transition
[MESH]
|Animals
[MESH]
|Apoptosis
[MESH]
|Breast Neoplasms/metabolism/*pathology
[MESH]
|Carcinogenesis
[MESH]
|Cell Movement
[MESH]
|Cell Proliferation
[MESH]
|Female
[MESH]
|Histocompatibility Antigens Class I/*metabolism
[MESH]
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