Both macrophages and hypoxia play critical role in regulating invasion of gastric cancer in vitro

Shen, Zhanlong; Kauttu, Tuuli; Seppänen, Hanna; Vainionpää, Sanna; Ye, Yingjiang; Wang, Shan; Mustonen, Harri; Puolakkainen, Pauli

doi:10.3109/0284186x.2012.718444

Cited by 31 publications

(29 citation statements)

References 23 publications

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“…While ADAM9 is regulated at the transcriptional level in monocytes and macrophages (3,10,55), ADAM9 is not regulated at the mRNA level in mature PMNs. ADAM9 is likely transcribed by PMN precursors in the bone marrow and stored as a performed proteinase within PMN granules and vesicles.…”

Section: Discussionmentioning

confidence: 99%

ADAM9 Is a Novel Product of Polymorphonuclear Neutrophils: Regulation of Expression and Contributions to Extracellular Matrix Protein Degradation during Acute Lung Injury

Roychaudhuri

Hergrueter

Polverino

et al. 2014

The Journal of Immunology

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A disintegrin and a metalloproteinase domain 9 (ADAM9**) is known to be expressed by monocytes and macrophages. Herein, we report that ADAM9 is also a product of human and murine polymorphonuclear neutrophils (PMNs). ADAM9 is not synthesized de novo by circulating PMNs. Rather, ADAM9 protein is stored in the gelatinase and specific granules and the secretory vesicles of human PMNs. Unstimulated PMNs express minimal quantities of surface ADAM9, but activation of PMNs with degranulating agonists rapidly (within 15 min) increases PMN surface ADAM9 levels. Human PMNs produce small quantities of soluble forms of ADAM9 (sADAM9). Surprisingly, ADAM9 degrades several extracellular matrix (ECM) proteins including fibronectin, entactin, laminin, and insoluble elastin as potently as MMP-9. However, ADAM9 does not degrade types I, III, or IV collagen, or denatured collagens in vitro. To determine whether Adam9 regulates PMN recruitment or ECM protein turnover during inflammatory responses, we compared wild type (WT) and Adam9−/− mice in bacterial lipopolysaccharide (LPS)- and bleomycin-mediated acute lung injury (ALI). Adam9 lung levels increase 10-fold during LPS-mediated ALI in WT mice (due to increases in leukocyte-derived Adam9), but Adam9 does not regulate lung PMN (or macrophage) counts during ALI. Adam9 increases mortality, promotes lung injury, reduces lung compliance, and increases degradation of lung elastin during LPS- and/or bleomycin-mediated ALI. Adam9 does not regulate collagen accumulation in the bleomycin-treated lung. Thus, ADAM9 is expressed in an inducible fashion on PMN surfaces where it degrades some ECM proteins, and promotes alveolar-capillary barrier injury during ALI in mice.

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Section: Discussionmentioning

confidence: 99%

ADAM9 Is a Novel Product of Polymorphonuclear Neutrophils: Regulation of Expression and Contributions to Extracellular Matrix Protein Degradation during Acute Lung Injury

Roychaudhuri

Hergrueter

Polverino

et al. 2014

The Journal of Immunology

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“…Another group looked at the role of tumor-associated macrophages (TAMs) in gastric cancer using a 3D dynamic migration imaging system to directly visualize the motility of tumor cells under normal and hypoxic conditions, both alone and in coculture with macrophages. They found that tumor cells in 3D culture (i) exhibit reduced migration speeds when under hypoxia; (ii) show increased migration rates when cocultured with macrophages; and most surprisingly; (iii) show a variable response when cocultured with macrophages under hypoxia where the migration speed of some cell lines increase under hypoxic conditions, while others decrease [32]. These apparently conflicting data emphasize that in vitro models do not converge on a set of coherent conclusions, suggesting that the phenotypes observed in vitro may be more a property of the model than the functions these cells actually exhibit in vivo and ultimate validation of any conclusion obtained from these in vitro assays must come from the ability to observe cell phenotypes, in vivo .…”

Section: Hypoxia Motility and Directionality In The Primary Tumormentioning

confidence: 99%

“…Importantly, comparison of the speeds reported in the few in vitro assays that measured this parameter [22,26,27,32,39,40] reveals that in vitro assays only recapitulate the slow migratory phenotype (Table 1). While treatment of the cells in culture to hypoxic conditions in some studies does result in an increase in migration rates, these elevated speeds still fall well within the slow migratory phenotype [35].…”

Section: Hypoxia Motility and Directionality In The Primary Tumormentioning

confidence: 99%

The Different Routes to Metastasis via Hypoxia-Regulated Programs

Nobre

Entenberg

Wang

et al. 2018

Trends in Cell Biology

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Hypoxia is linked to metastasis; however, how it affects metastatic progression is not clear due to limited consensus in the literature. We posit that this lack of consensus is due to hypoxia being studied using different approaches, such as in vitro, primary tumor, or metastasis assays in an isolated manner. Here, we review the pros and cons of in vitro hypoxia assays, highlight in vivo studies that inform on physiological hypoxia, and review the evidence that primary tumor hypoxia might influence the fate of disseminated tumor cells (DTCs) in secondary organs. Our analysis suggests that consensus can be reached by using in vivo methods of study, which also allow better modeling of how hypoxia affects DTC fate and metastasis.

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“…relatives (Qiu et al 2012;Cai et al 2013). With regard to ADAM9, previous study has showed that the mRNA and protein expression levels of this gene are elevated by the 14 regulation of reactive oxygen species under hypoxic stress conditions in prostate cancer cells (Shen et al 2013). In addition, hypoxia (1% oxygen) can also induce the 16 expression of ADAM9 in gastric cancer cells (Kim et al 2014).…”

Section: Signatures Of Deleterious Variation and Positive Selectionmentioning

confidence: 99%

Population Genomics Reveals Low Genetic Diversity and Adaptation to Hypoxia in Snub-Nosed Monkeys

et al. 2016

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Snub-nosed monkeys (genus Rhinopithecus) are a group of endangered colobines 2 endemic to South Asia. Here, we re-sequenced the whole genomes of 38 snub-nosed monkeys representing four species within this genus. By conducting population 4 genomic analyses, we observed an similar load of deleterious variation in snub-nosed monkeys living in both smaller and larger populations and found that genomic 6 diversity was lower than that reported in other primates. Reconstruction of Rhinopithecus evolutionary history suggested that episodes of climatic variation over 8 the past 2 million years, associated with glacial advances and retreats and population isolation, have shaped snub-nosed monkey demography and evolution. We further 10 identified several hypoxia-related genes under selection in R. bieti (black snub-nosed monkey), a species that exploits habitats higher than any other nonhuman primate. 12These results provide the first detailed and comprehensive genomic insights into genetic diversity, demography, genetic burden and adaptation in this radiation of 14 endangered primates. 16

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Both macrophages and hypoxia play critical role in regulating invasion of gastric cancer in vitro

Abstract: Both macrophages and hypoxia play an indispensable role in regulating the invasion of gastric cancer cells in vitro; ADAMs, MMP9 and TIMP3 might be involved in TAM induced invasive power of gastric cancer cells.

Cited by 31 publications

References 23 publications

ADAM9 Is a Novel Product of Polymorphonuclear Neutrophils: Regulation of Expression and Contributions to Extracellular Matrix Protein Degradation during Acute Lung Injury

ADAM9 Is a Novel Product of Polymorphonuclear Neutrophils: Regulation of Expression and Contributions to Extracellular Matrix Protein Degradation during Acute Lung Injury

The Different Routes to Metastasis via Hypoxia-Regulated Programs

Population Genomics Reveals Low Genetic Diversity and Adaptation to Hypoxia in Snub-Nosed Monkeys

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