Yao Dai1, Kyungmi Bae, Dietmar W Siemann. 1. Department of Radiation Oncology, University of Florida Shands Cancer Center, Gainesville, FL 32610, USA. daiyao@ufl.edu
Abstract
PURPOSE: Intratumoral hypoxia is known to be associated with radioresistance and metastasis. The present study examined the effect of acute and chronic hypoxia on the metastatic potential of prostate cancer PC-3, DU145, and LNCaP cells. METHODS AND MATERIALS: Cell proliferation and clonogenicity were tested by MTT assay and colony formation assay, respectively. "Wound-healing" and Matrigel-based chamber assays were used to monitor cell motility and invasion. Hypoxia-inducible factor 1 alpha (HIF-1α) expression was tested by Western blot, and HIF-1-target gene expression was detected by real-time polymerase chain reaction. Secretion of matrix metalloproteinases (MMPs) was determined by gelatin zymography. RESULTS: When PC-3 cells were exposed to 1% oxygen (hypoxia) for various periods of time, chronic hypoxia (≥24 h) decreased cell proliferation and induced cell death. In contrast, prostate cancer cells exposed to acute hypoxia (≤6 h) displayed increased motility, clonogenic survival, and invasive capacity. At the molecular level, both hypoxia and anoxia transiently stabilized HIF-1α. Exposure to hypoxia also induced the early expression of MMP-2, an invasiveness-related gene. Treatment with the HIF-1 inhibitor YC-1 attenuated the acute hypoxia-induced migration, invasion, and MMP-2 activity. CONCLUSIONS: The length of oxygen deprivation strongly affected the functional behavior of all three prostate cancer cell lines. Acute hypoxia in particular was found to promote a more aggressive metastatic phenotype. Published by Elsevier Inc.
PURPOSE: Intratumoral hypoxia is known to be associated with radioresistance and metastasis. The present study examined the effect of acute and chronic hypoxia on the metastatic potential of prostate cancerPC-3, DU145, and LNCaP cells. METHODS AND MATERIALS: Cell proliferation and clonogenicity were tested by MTT assay and colony formation assay, respectively. "Wound-healing" and Matrigel-based chamber assays were used to monitor cell motility and invasion. Hypoxia-inducible factor 1 alpha (HIF-1α) expression was tested by Western blot, and HIF-1-target gene expression was detected by real-time polymerase chain reaction. Secretion of matrix metalloproteinases (MMPs) was determined by gelatin zymography. RESULTS: When PC-3 cells were exposed to 1% oxygen (hypoxia) for various periods of time, chronic hypoxia (≥24 h) decreased cell proliferation and induced cell death. In contrast, prostate cancer cells exposed to acute hypoxia (≤6 h) displayed increased motility, clonogenic survival, and invasive capacity. At the molecular level, both hypoxia and anoxia transiently stabilized HIF-1α. Exposure to hypoxia also induced the early expression of MMP-2, an invasiveness-related gene. Treatment with the HIF-1 inhibitor YC-1 attenuated the acute hypoxia-induced migration, invasion, and MMP-2 activity. CONCLUSIONS: The length of oxygen deprivation strongly affected the functional behavior of all three prostate cancer cell lines. Acute hypoxia in particular was found to promote a more aggressive metastatic phenotype. Published by Elsevier Inc.
Authors: Selma Pennacchietti; Paolo Michieli; Maria Galluzzo; Massimiliano Mazzone; Silvia Giordano; Paolo M Comoglio Journal: Cancer Cell Date: 2003-04 Impact factor: 31.743
Authors: H Zhong; A M De Marzo; E Laughner; M Lim; D A Hilton; D Zagzag; P Buechler; W B Isaacs; G L Semenza; J W Simons Journal: Cancer Res Date: 1999-11-15 Impact factor: 12.701
Authors: O Thews; T Wolloscheck; W Dillenburg; S Kraus; D K Kelleher; M A Konerding; P Vaupel Journal: Br J Cancer Date: 2004-09-13 Impact factor: 7.640