Abstract
Prostate cancer metastasis has an enormous impact on the mortality of cancer patients. Factors involved in cancer progression and metastasis are known to be key players in microgravity (µg)-driven three-dimensional (3D) cancer spheroid formation. We investigated PC-3 prostate cancer cells for 30 min, 2, 4 and 24 h on the random positioning machine (RPM), a device simulating µg on Earth. After a 24 h RPM-exposure, the cells could be divided into two groups: one grew as 3D multicellular spheroids (MCS), the other one as adherent monolayer (AD). No signs of apoptosis were visible. Among others, we focused on cytokines involved in the events of metastasis and MCS formation. After 24 h of exposure, in the MCS group we measured an increase in ACTB, MSN, COL1A1, LAMA3, FN1, TIMP1, FLT1, EGFR1, IL1A, IL6, CXCL8, and HIF1A mRNA expression, and in the AD group an elevation of LAMA3, COL1A1, FN1, MMP9, VEGFA, IL6, and CXCL8 mRNAs compared to samples subjected to 1 g conditions. Significant downregulations in AD cells were detected in the mRNA levels of TUBB, KRT8, IL1B, IL7, PIK3CB, AKT1 and MTOR after 24 h. The release of collagen-1α1 and fibronectin protein in the supernatant was decreased, whereas the secretion of IL-6 was elevated in 24 h RPM samples. The secretion of IL-1α, IL-1β, IL-7, IL-2, IL-8, IL-17, TNF-α, laminin, MMP-2, TIMP-1, osteopontin and EGF was not significantly altered after 24 h compared to 1 g conditions. The release of soluble factors was significantly reduced after 2 h (IL-1α, IL-2, IL-7, IL-8, IL-17, TNF-α, collagen-1α1, MMP-2, osteopontin) and elevated after 4 h (IL-1β, IL-2, IL-6, IL-7, IL-8, TNF-α, laminin) in RPM samples. Taken together, simulated µg induced 3D growth of PC-3 cancer cells combined with a differential expression of the cytokines IL-1α, IL-1β, IL-6 and IL-8, supporting their involvement in growth and progression of prostate cancer cells.
Highlights
As estimated by GLOBOCAN (Global Cancer Observatory) in 2020, prostate cancer (PC) comprises an incidence of almost 1.4 million new cases and 375,000 deaths worldwide (Sung et al, 2021)
In this study we investigated the impact of short-term (30 min, 2, 4 and 24 h) s-μg-exposure via random positioning machine (RPM) on PC-3 prostate cancer cells, which were established from an adenocarcinoma
There are two different phenotypes of PC-3 cells visible: adherently growing cells (AD) and detached 3D multicellular spheroids (MCS) (Figures 1B,C) We used a “terminal deoxynucleotidyl transferase dUTP nick end labeling” (TUNEL) assay to detect DNA breaks formed during the final phase of apoptosis, when DNA fragmentation takes place
Summary
As estimated by GLOBOCAN (Global Cancer Observatory) in 2020, prostate cancer (PC) comprises an incidence of almost 1.4 million new cases and 375,000 deaths worldwide (Sung et al, 2021). The 5-years survival rate for most men with local or regional PC is nearly 100%, but if diagnosed with PC metastasis, the 5-years survival rate is reduced to 31% (Gandaglia et al, 2014). This shows that metastasis of PC has a vast impact on the mortality and the overall quality of life of patients. There is an urgent need to increase the knowledge of PC biology, genomics, proteomics and advanced profiling technologies in order to find new drug development targets
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