Hypoxia: Signaling the Metastatic Cascade

Rankin, Erinn B.; Nam, Jin Min; Giaccia, Amato J.

doi:10.1016/j.trecan.2016.05.006

Cited by 181 publications

(149 citation statements)

References 91 publications

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“…Furthermore, hypoxia or oxygen deficiency is a prominent feature of solid tumours. Hypoxic tumours are often resistant to conventional cancer therapies, and tumour hypoxia correlates with advanced stages of malignancy and metastasis . We further investigated the potential lncRNAs regulated by hypoxia.…”

Section: Resultsmentioning

confidence: 99%

“…Hypoxic tumours are often resistant to conventional cancer therapies, and tumour hypoxia correlates with advanced stages of malignancy and metastasis. [20][21][22] We further investigated the potential lncRNAs regulated by hypoxia. KP cells were cultured in normoxia (20% O 2 ) vs hypoxia (1% O 2 ) for up to 48 hours, and Western blotting showed that hypoxia effectively The LLCN contained a total of 4086 lncRNAs with 19 595 edges between them ( Figure 6C, Table S6, S7).…”

Section: Analysis Of Lncrnas Associated With P53 Kras or Hypoxiamentioning

confidence: 99%

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Deregulated lncRNA expression profile in the mouse lung adenocarcinomas with KRAS‐G12D mutation and P53 knockout

Zhang

Jiang

Cui

et al. 2019

J Cellular Molecular Medi

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Recent studies have demonstrated that aberrant long non‐coding RNAs (lncRNAs) expression are suggested to be closely associated with multiple human diseases, lung cancer included. However, the roles of lncRNAs in lung cancer are not well understood. In this study, we used microarrays to investigate the aberrantly expressed lncRNAs in the mouse lung adenocarcinoma with P53 knockout and the KrasG12D mutation. Results revealed that 6424 lncRNAs were differentially expressed (≥ 2‐fold change, P < .05). Two hundred and ten lncRNAs showed more than 8‐fold change and conserved across human and were further analysed in the primary mouse lung adenocarcinoma KP cells, which were isolated from the p53 knockout and the KrasG12D mutation mice. Among all the 210 lncRNAs, 11 lncRNAs' expression was regulated by P53, 33 lncRNAs by KRAS and 13 lncRNAs by hypoxia in the primary KP cells, respectively. NONMMUT015812, which was remarkably up‐regulated in the mouse lung adenocarcinoma and negatively regulated by the P53 re‐expression, was detected to analyse its cellular function. Results showed that knockdown of NONMMUT015812 by shRNAs decreased proliferation and migration abilities of KP cells. Among those aberrantly expressed lncRNAs in the mouse lung adenocarcinoma, NONMMUT015812 was a potential oncogene.

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Section: Resultsmentioning

confidence: 99%

Section: Analysis Of Lncrnas Associated With P53 Kras or Hypoxiamentioning

confidence: 99%

Deregulated lncRNA expression profile in the mouse lung adenocarcinomas with KRAS‐G12D mutation and P53 knockout

Zhang

Jiang

Cui

et al. 2019

J Cellular Molecular Medi

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“…3,5,7,8,20,[26][27][28][29] Key molecular players in PMN preparation include MMPs, vascular endothelial growth factors, placental growth factor, tumor necrosis factor 1 alpha (TNF1α), transforming growth factor beta (TGFβ), and LOX 3,[5][6][7]20,27 ; notably, hypoxia regulates the expression of several of them. 20,22,30,31 We have also reported that exosomes secreted by human PCa cells under hypoxia are loaded with several of these growth factors and cytokines (TNF1α, TGFβ, and interleukin 6) along with higher MMP (2 and 9) activity. 22 Based upon that, in the present study we assessed the in vivo effect of exosomes secreted by human PCa PC3 cells under hypoxia on various biomarkers associated with PMN.…”

Section: Introductionmentioning

confidence: 90%

“…The well characterized hallmarks of PMN include: (a) extensive extracellular matrix (ECM) remodeling including higher matrix metalloproteinases (MMPs) activity as well as accumulation of fibronectin, collagen, growth factors and chemoattractants; (b) immunosuppressive and proinflammatory milieu including an increase in the infiltration of bone marrow derived cells (BMDCs); and (c) higher vascular leakiness, 3,5,7,8,20,26–29 . Key molecular players in PMN preparation include MMPs, vascular endothelial growth factors, placental growth factor, tumor necrosis factor 1 alpha (TNF1α), transforming growth factor beta (TGFβ), and LOX 3,5–7,20,27 ; notably, hypoxia regulates the expression of several of them 20,22,30,31 . We have also reported that exosomes secreted by human PCa cells under hypoxia are loaded with several of these growth factors and cytokines (TNF1α, TGFβ, and interleukin 6) along with higher MMP (2 and 9) activity 22 .…”

Section: Introductionmentioning

confidence: 99%

Exosomes secreted by prostate cancer cells under hypoxia promote matrix metalloproteinases activity at pre‐metastatic niches

Deep

Jain

Kumar

et al. 2020

Molecular Carcinogenesis

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Approximately, 30 000 men die from prostate cancer (PCa) every year in the United States, mainly due to the metastasis. Thus, the key events associated with PCa metastasis are under rigorous investigation, with recent studies showing that preparation of pre‐metastatic niches (PMN) in distant organs is an important step. However, the molecular basis for PMN preparation is still unclear. Hypoxia in primary tumors promotes aggressiveness; however, its precise role in metastasis is not clear. We recently reported that exosomes secreted by PCa cells under hypoxia promote stemness and invasiveness in naïve PCa cells; however, whether these extracellular vesicles also influence PMN remains unknown. In the present study, we isolated exosomes from human PCa PC3 cells under normoxic (21% O2, exosomes secreted under normoxic condition [ExoNormoxic]) and hypoxic (1% O2, exosomes secreted under hypoxic condition [ExoHypoxic]) conditions, and characterized their effect (10 µg exosomes, intraperitoneal (IP) treatment every 48 hours for 4 weeks) on key biomarkers associated with PMN in nude mice. Whole animal fluorescence imaging showed that ExoHypoxic treatment promotes matrix metalloproteinases (MMPs) activity in several putative metastatic sites. Histological studies confirmed that ExoHypoxic treatment enhanced the level of MMP2, MMP9, and extracellular matrix proteins (fibronectin and collagen) as well as increased the number of CD11b+ cells at selective PMN sites. Furthermore, proteomic profiling of exosomes by liquid chromatography/mass spectrometry identified cargo proteins in ExoNormoxic and ExoHypoxic as well as distinct canonical pathways targeted by them. These results suggest that exosomes secreted by PCa cells under hypoxia plausibly remodel distant PMN, and thus, could be a potential target to control metastatic PCa.

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“…A hypoxia microenvironment within tumor tissues can not only suppress the efficacies of chemotherapy and oxygen-dependent photodynamic therapies to increase the survival rates of cancer cells, and thus the tumor recurrent probabilities, but also promote the metastasis of cancer cells from tumor tissues. [5,6] Therefore, development of long NIR light-initiated oxygen-independent PDT able to generate ROS under an oxygen-deprived condition to kill cancer cells within hypoxia tumor microdomains is very crucial to suppress tumor recurrent and metastasis. In the literature, fluorinated nanoplatforms, PL-W 18 O 49 -TPZ nanoparticles and nano perfluorocarbons (PFC), were reported as anticancer agents to overcome hypoxia.…”

Section: Doi: 101002/ppsc202000001mentioning

confidence: 99%

Size and Shape Effects of Near‐Infrared Light‐Activatable Cu₂(OH)PO₄ Nanostructures on Phototherapeutic Destruction of Drug‐Resistant Hypoxia Tumors

Nuthalapati

Vankayala

Chiang

et al. 2020

Part & Part Syst Charact

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Development of simple, robust, and noninvasive therapeutic approaches to treat cancers and improve survival rates is a grand challenge in clinical biomedicine. In particular, the sizes and shape of the nanomaterials play a vital role in dictating their biodistribution and clearance pathways. It remains elusive how the size and shape of a nanomaterial affect its therapeutic efficacy in cancer diagnosis and treatments. To tackle the above problem, the effects of size and shape of Cu2(OH)PO4 nanostructures (nanosheets and quantum dots) on the photodynamic therapy (PDT) in destroying malignant drug‐resistant lung tumors and on combating the tumor hypoxia problem are investigated and compared. The photocatalytic mechanism of Cu2(OH)PO4 nanostructures mainly involves the generation of reactive oxygen species (ROS), such as hydroxyl radical (·OH) and singlet oxygen (1O2). Under an oxygen deprivation condition, Cu2(OH)PO4 nanosheets still can generate OH radicals to kill cancer cells upon near‐infrared (NIR) light irradiation. Overall, in vitro and in vivo experiments show that Cu2(OH)PO4 nanosheets can overcome tumor hypoxia problems and effectively mediate dual modal PDT and photothermal therapeutic (PTT) effects on destruction of NCI‐H23 lung tumors in mice using ultralow doses (350 mW cm−2) of NIR (915 nm) light.

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Hypoxia: Signaling the Metastatic Cascade

Cited by 181 publications

References 91 publications

Deregulated lncRNA expression profile in the mouse lung adenocarcinomas with KRAS‐G12D mutation and P53 knockout

Deregulated lncRNA expression profile in the mouse lung adenocarcinomas with KRAS‐G12D mutation and P53 knockout

Exosomes secreted by prostate cancer cells under hypoxia promote matrix metalloproteinases activity at pre‐metastatic niches

Size and Shape Effects of Near‐Infrared Light‐Activatable Cu₂(OH)PO₄ Nanostructures on Phototherapeutic Destruction of Drug‐Resistant Hypoxia Tumors

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Hypoxia: Signaling the Metastatic Cascade

Cited by 181 publications

References 91 publications

Deregulated lncRNA expression profile in the mouse lung adenocarcinomas with KRAS‐G12D mutation and P53 knockout

Deregulated lncRNA expression profile in the mouse lung adenocarcinomas with KRAS‐G12D mutation and P53 knockout

Exosomes secreted by prostate cancer cells under hypoxia promote matrix metalloproteinases activity at pre‐metastatic niches

Size and Shape Effects of Near‐Infrared Light‐Activatable Cu2(OH)PO4 Nanostructures on Phototherapeutic Destruction of Drug‐Resistant Hypoxia Tumors

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About

Size and Shape Effects of Near‐Infrared Light‐Activatable Cu₂(OH)PO₄ Nanostructures on Phototherapeutic Destruction of Drug‐Resistant Hypoxia Tumors