Prostate Cancer Cell Lines under Hypoxia Exhibit Greater Stem-Like Properties

Abstract

Hypoxia is an important environmental change in many cancers. Hypoxic niches can be occupied by cancer stem/progenitor-like cells that are associated with tumor progression and resistance to radiotherapy and chemotherapy. However, it has not yet been fully elucidated how hypoxia influences the stem-like properties of prostate cancer cells. In this report, we investigated the effects of hypoxia on human prostate cancer cell lines, PC-3 and DU145. In comparison to normoxia (20% O2), 7% O2 induced higher expressions of HIF-1α and HIF-2α, which were associated with upregulation of Oct3/4 and Nanog; 1% O2 induced even greater levels of these factors. The upregulated NANOG mRNA expression in hypoxia was confirmed to be predominantly retrogene NANOGP8. Similar growth rates were observed for cells cultivated under hypoxic and normoxic conditions for 48 hours; however, the colony formation assay revealed that 48 hours of hypoxic pretreatment resulted in the formation of more colonies. Treatment with 1% O2 also extended the G0/G1 stage, resulting in more side population cells, and induced CD44 and ABCG2 expressions. Hypoxia also increased the number of cells positive for ABCG2 expression, which were predominantly found to be CD44bright cells. Correspondingly, the sorted CD44bright cells expressed higher levels of ABCG2, Oct3/4, and Nanog than CD44dim cells, and hypoxic pretreatment significantly increased the expressions of these factors. CD44bright cells under normoxia formed significantly more colonies and spheres compared with the CD44dim cells, and hypoxic pretreatment even increased this effect. Our data indicate that prostate cancer cells under hypoxia possess greater stem-like properties.

The Nf-κb Inhibitor Imd-0354 Targets Human Non-Small Cell Lung Cancer Stem Cells and Combined with Chemotherapy Reduces Multidrug Resistance

“…These CSCs also exhibited other characteristic stem cell-like properties: tumor-sphere formation in low attachment plates, and expression of Oct4, Nanog, Sox2 and Survivin stem-ness related genes. Interestingly, SP of CSCs in A549Luc cells increased under hypoxia, similarly to what has been found in ovarian and prostate cancer [62,63].…”

Unconventional ratiometric-enhanced optical sensing of oxygen by mixed-phase TiO2

“…In fact, DO content in cell culture media affects cell growth rate, metabolism and protein synthesis, exerting a decisive influence on the cellular functions and behaviors. To mention a few examples, hypoxia/re-oxygenation induce stem cell like phenotype in prostate cancer cells 5 and enhance the proliferation, invasiveness and metastatic potential of tumor cells 6,7 , while hyperoxia can cause cell death via the formation of reactive oxygen species 8,9 .…”

Oncogenic mutational/epigenetic events: Deterministic, stochastic or random: Implications for hypoxic cancer cells and tumor heterogeneity

“…To the extent this modulation involved any of the 12 major driver categories and signaling pathways affecting cell survival, fate and genomic integrity [1] or programming that directs differentiation, genetically or phenotypically dissimilar clones should result. This could be especially true of cells subjected to hypoxic or other forms of stress [31][32][33][34].…”