Hypoxia and TGF-β1 lead to endostatin resistance by cooperatively increasing cancer stem cells in A549 transplantation tumors

AbstractPurposeIn prostate cancer, castration resistance is a factor that frequently leads to death in individuals with this disease. Recent studies have suggested that prostate cancer stem cells (PCSCs) are pivotal regulators in the establishment of castration resistance. The nanog homeobox (NANOG) and the transforming growth factor (TGF)-β1/drosophila mothers against decapentaplegic protein (SMAD) signaling pathways are involved in several cancer stem cells but are not involved in PCSCs. The purpose of this study is to investigate the effect of NANOG on the proliferation of PCSCs regulated by the TGF-β1/SMAD signaling pathway.MethodsIn this study, we used flow cytometry to isolate CD44+/CD133+/NANOG+ PCSCs from DU145 prostate cancer cells. Then we used short hairpin RNA to silence NANOG and observed the biological behavior and the TGF-β1/SMAD signal of PCSCs.ResultsNANOG decreased PCSC proliferation, increased apoptosis, and blocked cell cycling at G0/G1. Furthermore, reduction in the TGF-β1, p15, and p-SMAD2 expression was observed.ConclusionThese findings suggest that NANOG positively regulates the growth of PCSCs through the TGF-β1/SMAD signaling pathway.

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Effects of umbilical cord- and adipose-derived stem cell secretomes on ALDH1A3 expression and autocrine TGF-β1 signaling in human breast cancer stem cells

F1000Research ◽

10.12688/f1000research.13609.1 ◽

2018 ◽

Vol 7 ◽

pp. 249 ◽

Cited By ~ 1

Author(s):

Purnamawati Purnamawati ◽

Jeanne Adiwinata Pawitan ◽

Andhika Rachman ◽

Septelia Inawati Wanandi

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Umbilical Cord ◽

Human Breast Cancer ◽

Published Data ◽

Type I ◽

Breast Cancer Stem Cells ◽

Human Breast ◽

Tgf Β1

Background: Nowadays, umbilical cord- and adipose-derived stem cells (UCSCs and ASCs) are the most common sources of mesenchymal stem cells (MSCs). As part of the tumor microenvironment, MSCs are known to communicate with cancer cells via their secretomes. Increased activity of aldehyde dehydrogenase-1 (ALDH1) has been widely used as a common intrinsic stemness marker in normal and cancer stem cells. Our study aimed to elaborate on the effect of UCSC and ASC secretomes on the expression of ALDH1A3, as one of the important variants of ALDH1, TGF-β1 and TGF-β receptor type I (TβRI) in human breast cancer stem cells (BCSCs). Methods: UCSCs and ASCs were cultured in serum-free α-MEM media under standard conditions for 24 hours. The conditioned medium (CM) containing secretomes of UCSCs and ASCs were collected and added 50% (v/v) to the cultured of human BCSCs for 72 hours. The mRNA expressions of ALDH1A3, TGF-β1, and TβRI were determined using quantitative Reverse Transcriptase Polymerase Chain Reaction (q-RT-PCR). Results: We found that CM of UCSCs significantly increased the ALDH1A3 expression of BCSCs in parallel with the increase of TGF-β1 and TβRI expressions. Conversely, CM of ASCs had no significant effect on the ALDH1A3 expression, but significantly decreased TGF-β1 and TβRI expressions of BCSCs. These results contradict our published data on ALDH1A1, which is another important variant of ALDH1, as well as data of the pluripotency markers OCT4 and SOX2 expressions. Conclusions: UCSC and ASC secretomes have different regulation on ALDH1A3 expression in human BCSCs, which may be related to the autocrine TGF-β1 signaling in modulating cell proliferation and stemness of BCSCs. Further studies are required to evaluate factors involved in the differential effects of UCSC and ASC secretomes that regulate ALDH1A3 expression in relation to autocrine TGF-β1 signaling and aggressiveness of human BCSCs.

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