title: Characterization of phosphoglycerate kinase-1 expression of stromal cells derived from tumor microenvironment in prostate cancer progression.
abstract: 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.
authors.affiliation: Institute of Medical Sciences, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, PR. China. jianhuaw2007@gmail.com
authors.forename: Jianhua
authors.initials: J
authors.lastname: Wang
authors.forename: Gigi
authors.initials: G
authors.lastname: Ying
authors.forename: Jingchen
authors.initials: J
authors.lastname: Wang
authors.forename: Younghun
authors.initials: Y
authors.lastname: Jung
authors.forename: Jian
authors.initials: J
authors.lastname: Lu
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhu
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Pienta
authors.forename: Russell S
authors.initials: RS
authors.lastname: Taichman
mesh_terms: 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
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D010735:Phosphoglycerate Kinase