TY - JOUR
T1 - CD10-equipped melanoma cells acquire highly potent tumorigenic activity
T2 - A plausible explanation of their significance for a poor prognosis
AU - Oba, Junna
AU - Nakahara, Takeshi
AU - Hashimoto-Hachiya, Akiko
AU - Liu, Min
AU - Abe, Takeru
AU - Hagihara, Akihito
AU - Yokomizo, Takehiko
AU - Furue, Masutaka
N1 - Funding Information:
We appreciate the technical support from the Research Support Center, Kyushu University. The microarray analysis was supported by World Fusion Co., Ltd.
Publisher Copyright:
© 2016 Oba et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/2
Y1 - 2016/2
N2 - CD10 has been widely used in cancer diagnosis. We previously demonstrated that its expression in melanoma increased with tumor progression and predicted poor patient survival. However, the mechanism by which CD10 promotes melanoma progression remains unclear. In order to elucidate the role of CD10 in melanoma, we established CD10-overexpressing A375 melanoma cells and performed DNA microarray and qRT-PCR analyses to identify changes in the gene expression profile. The microarray analysis revealed that upregulated genes in CD10-A375 were mostly involved in cell proliferation, angiogenesis, and resistance to apoptosis; down-regulated genes mostly belonged to the categories associated with cell adhesion and migration. Accordingly, in functional experiments, CD10-A375 showed significantly greater cell proliferation in vitro and higher tumorigenicity in vivo; CD10 enzymatic inhibitors, thiorphan and phosphoramidon, significantly blocked the tumor growth of CD10-A375 in mice. In migration and invasion assays, CD10-A375 displayed lower migratory and invasive capacity than mock-A375. CD10 augmented melanoma cell resistance to apoptosis mediated by etoposide and gemcitabine. These findings indicate that CD10 may promote tumor progression by regulating the expression profiles of genes related to cell proliferation, angiogenesis, and resistance to apoptosis.
AB - CD10 has been widely used in cancer diagnosis. We previously demonstrated that its expression in melanoma increased with tumor progression and predicted poor patient survival. However, the mechanism by which CD10 promotes melanoma progression remains unclear. In order to elucidate the role of CD10 in melanoma, we established CD10-overexpressing A375 melanoma cells and performed DNA microarray and qRT-PCR analyses to identify changes in the gene expression profile. The microarray analysis revealed that upregulated genes in CD10-A375 were mostly involved in cell proliferation, angiogenesis, and resistance to apoptosis; down-regulated genes mostly belonged to the categories associated with cell adhesion and migration. Accordingly, in functional experiments, CD10-A375 showed significantly greater cell proliferation in vitro and higher tumorigenicity in vivo; CD10 enzymatic inhibitors, thiorphan and phosphoramidon, significantly blocked the tumor growth of CD10-A375 in mice. In migration and invasion assays, CD10-A375 displayed lower migratory and invasive capacity than mock-A375. CD10 augmented melanoma cell resistance to apoptosis mediated by etoposide and gemcitabine. These findings indicate that CD10 may promote tumor progression by regulating the expression profiles of genes related to cell proliferation, angiogenesis, and resistance to apoptosis.
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U2 - 10.1371/journal.pone.0149285
DO - 10.1371/journal.pone.0149285
M3 - Article
C2 - 26881775
AN - SCOPUS:84960539259
SN - 1932-6203
VL - 11
JO - PloS one
JF - PloS one
IS - 2
M1 - e0149285
ER -