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Characterization of Phosphoglycerate Kinase-1 Expression of Stromal Cells Derived from Tumor Microenvironment in Prostate Cancer Progression
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Zeitschriftentitel: | Cancer Research |
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Personen und Körperschaften: | , , , , , , , |
In: | Cancer Research, 70, 2010, 2, S. 471-480 |
Format: | E-Article |
Sprache: | Englisch |
veröffentlicht: |
American Association for Cancer Research (AACR)
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Schlagwörter: |
Zusammenfassung: | <jats:title>Abstract</jats:title> <jats:p>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 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. Cancer Res; 70(2); 471–80</jats:p> |
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Umfang: | 471-480 |
ISSN: |
0008-5472
1538-7445 |
DOI: | 10.1158/0008-5472.can-09-2863 |