TY - JOUR
T1 - Characterization of phosphoglycerate kinase-1 expression of stromal cells derived from tumor microenvironment in prostate cancer progression
AU - Wang, Jianhua
AU - Ying, Gigi
AU - Wang, Jingchen
AU - Jung, Younghun
AU - Lu, Jian
AU - Zhu, Jiang
AU - Pienta, Kenneth J.
AU - Taichman, Russell S.
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2010/1/15
Y1 - 2010/1/15
N2 - Tumor and stromal interactions in the tumor microenvironment are critical for oncogenesis and cancer progression. Our understanding of the molecular events by which reactive stromal fibroblasts - myofibroblast or cancer-associated fibroblasts (CAF) - affect the growth and invasion of prostate cancer remains unclear. Laser capture microdissection and cDNA microarray analysis of CAFs in prostate tumors revealed strong up-regulation of phosphoglycerate kinase-1 (PGK1), an ATP-generating glycolytic enzyme that forms part of the glycolytic pathway and is directly involved in CXCL12-CXCR4 signaling. Normal fibroblasts overexpressing PGK1 resembled myofibroblasts in their expression of smooth muscle α-actin, vimentin, and high levels of CXCL12. These cells also displayed a higher proliferative index and the capability to contribute to prostate tumor cell invasion in vitro, possibly through expression of MMP-2 and MMP-3 and activation of the AKT and ERK pathways. Coimplantation of PGK1-overexpressing fibroblasts with prostate tumor cells promoted tumor cell growth in vivo. Collectively, these observations suggest that PGK1 helps support the interactions between cancer and its microenvironment.
AB - Tumor and stromal interactions in the tumor microenvironment are critical for oncogenesis and cancer progression. Our understanding of the molecular events by which reactive stromal fibroblasts - myofibroblast or cancer-associated fibroblasts (CAF) - affect the growth and invasion of prostate cancer remains unclear. Laser capture microdissection and cDNA microarray analysis of CAFs in prostate tumors revealed strong up-regulation of phosphoglycerate kinase-1 (PGK1), an ATP-generating glycolytic enzyme that forms part of the glycolytic pathway and is directly involved in CXCL12-CXCR4 signaling. Normal fibroblasts overexpressing PGK1 resembled myofibroblasts in their expression of smooth muscle α-actin, vimentin, and high levels of CXCL12. These cells also displayed a higher proliferative index and the capability to contribute to prostate tumor cell invasion in vitro, possibly through expression of MMP-2 and MMP-3 and activation of the AKT and ERK pathways. Coimplantation of PGK1-overexpressing fibroblasts with prostate tumor cells promoted tumor cell growth in vivo. Collectively, these observations suggest that PGK1 helps support the interactions between cancer and its microenvironment.
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U2 - 10.1158/0008-5472.CAN-09-2863
DO - 10.1158/0008-5472.CAN-09-2863
M3 - Article
C2 - 20068185
AN - SCOPUS:76549084854
VL - 70
SP - 471
EP - 480
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 2
ER -