Characterization of phosphoglycerate kinase-1 expression of stromal cells derived from tumor microenvironment in prostate cancer progression.
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 upregulation 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 alpha-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.
Wang
Jianhua
J
Institute of Medical Sciences, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, PR. China. jianhuaw2007@gmail.com
Ying
Gigi
G
Wang
Jingchen
J
Jung
Younghun
Y
Lu
Jian
J
Zhu
Jiang
J
Pienta
Kenneth J
KJ
Taichman
Russell S
RS
D000199:Actins / Q000378:metabolism; D000818:Animals; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000096:biosynthesis / Q000378:metabolism; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D010735:Phosphoglycerate Kinase / Q000096:biosynthesis*; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D017154:Stromal Cells / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation
C541116:ACTA2 protein, human; D000199:Actins; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D010735:Phosphoglycerate Kinase