Tumor-associated macrophages induce invasion and poor prognosis in human gastric cancer in a cyclooxygenase-2/MMP9-dependent manner. Article Swipe
Ji Xu
,
Yajuan Yu
,
Xujun He
,
Nan Niu
,
Xiao Li
,
Renchao Zhang
,
Junfeng Hu
,
Jie Ma
,
Xiaojun Yu
,
Yuanshui Sun
,
Haibin Ni
,
Fengyong Wang
·
YOU?
·
· 2019
· Open Access
·
YOU?
·
· 2019
· Open Access
·
Cyclooxygenase-2 (COX2) and tumor-associated macrophages (TAMs) are associated with invasion, angiogenesis, and poor prognosis in many human cancers. However, the role of TAMs in human gastric cancer (GC) remains elusive. In the present study, we first measured COX2 expression and TAM infiltration in human GC tissues using double immunohistochemical staining. Then, we indirectly cocultured M2-polarized macrophages derived from human THP-1 cells with GC cells as an in vitro model. Transwell assays, siRNA transfection, treatment with a COX2 inhibitor and Western blotting were used to investigate the relationship among TAMs, invasion and COX2 expression as well as the underlying molecular mechanism. Double IHC staining showed that TAMs were aggregated near GC tumor nests and had high COX2 expression; moreover, the number of TAMs that infiltrated the tumor nest was correlated with the depth of invasion, COX2 expression and poor prognosis in human GC. In an in vitro assay, after treatment with phorbol myristate acetate (PMA), the THP-1 cells differentiated into M2 macrophages and induced COX2/MMP9-dependent invasiveness in GC cells. Pretreatment of GC cells with COX2 siRNA or a COX2 inhibitor (Celecoxib) can negate these promoting effects. The results of this study and those of our previous studies indicate that coculture with M2-polarized macrophages can induce the COX2-dependent release of matrix metalloproteinase-9 (MMP9), which subsequently increases the invasiveness of GC cells. Our data may provide a basis for targeting TAMs or for polarizing TAMs through immune regulation to halt GC progression, which could soon become a nonsurgical treatment for human gastric cancer.
Related Topics
Concepts
MMP9
Cancer research
Immunohistochemistry
Matrix metalloproteinase
Transfection
In vitro
Cancer cell
Gentamicin protection assay
Angiogenesis
Cyclooxygenase
Cancer
Chemistry
Cell culture
Biology
Medicine
Downregulation and upregulation
Immunology
Metastasis
Enzyme
Internal medicine
Biochemistry
Gene
Genetics
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://pubmed.ncbi.nlm.nih.gov/31632572
- OA Status
- green
- Cited By
- 58
- References
- 40
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2986861431
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W2986861431Canonical identifier for this work in OpenAlex
- Title
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Tumor-associated macrophages induce invasion and poor prognosis in human gastric cancer in a cyclooxygenase-2/MMP9-dependent manner.Work title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2019Year of publication
- Publication date
-
2019-01-01Full publication date if available
- Authors
-
Ji Xu, Yajuan Yu, Xujun He, Nan Niu, Xiao Li, Renchao Zhang, Junfeng Hu, Jie Ma, Xiaojun Yu, Yuanshui Sun, Haibin Ni, Fengyong WangList of authors in order
- Landing page
-
https://pubmed.ncbi.nlm.nih.gov/31632572Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.ncbi.nlm.nih.gov/pmc/articles/6789263Direct OA link when available
- Concepts
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MMP9, Cancer research, Immunohistochemistry, Matrix metalloproteinase, Transfection, In vitro, Cancer cell, Gentamicin protection assay, Angiogenesis, Cyclooxygenase, Cancer, Chemistry, Cell culture, Biology, Medicine, Downregulation and upregulation, Immunology, Metastasis, Enzyme, Internal medicine, Biochemistry, Gene, GeneticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
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58Total citation count in OpenAlex
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2025: 10, 2024: 5, 2023: 8, 2022: 6, 2021: 16Per-year citation counts (last 5 years)
- References (count)
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40Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.measured | 36 |
| abstract_inverted_index.previous | 194 |
| abstract_inverted_index.staining | 102 |
| abstract_inverted_index.Transwell | 69 |
| abstract_inverted_index.coculture | 198 |
| abstract_inverted_index.increases | 213 |
| abstract_inverted_index.inhibitor | 77, 178 |
| abstract_inverted_index.invasion, | 9, 133 |
| abstract_inverted_index.molecular | 98 |
| abstract_inverted_index.moreover, | 117 |
| abstract_inverted_index.myristate | 151 |
| abstract_inverted_index.prognosis | 13, 138 |
| abstract_inverted_index.promoting | 183 |
| abstract_inverted_index.staining. | 49 |
| abstract_inverted_index.targeting | 226 |
| abstract_inverted_index.treatment | 73, 148, 245 |
| abstract_inverted_index.aggregated | 107 |
| abstract_inverted_index.associated | 7 |
| abstract_inverted_index.cocultured | 53 |
| abstract_inverted_index.correlated | 128 |
| abstract_inverted_index.expression | 38, 92, 135 |
| abstract_inverted_index.indirectly | 52 |
| abstract_inverted_index.mechanism. | 99 |
| abstract_inverted_index.polarizing | 230 |
| abstract_inverted_index.regulation | 234 |
| abstract_inverted_index.underlying | 97 |
| abstract_inverted_index.(Celecoxib) | 179 |
| abstract_inverted_index.expression; | 116 |
| abstract_inverted_index.infiltrated | 123 |
| abstract_inverted_index.investigate | 84 |
| abstract_inverted_index.macrophages | 4, 55, 160, 201 |
| abstract_inverted_index.nonsurgical | 244 |
| abstract_inverted_index.M2-polarized | 54, 200 |
| abstract_inverted_index.Pretreatment | 168 |
| abstract_inverted_index.infiltration | 41 |
| abstract_inverted_index.invasiveness | 164, 215 |
| abstract_inverted_index.progression, | 238 |
| abstract_inverted_index.relationship | 86 |
| abstract_inverted_index.subsequently | 212 |
| abstract_inverted_index.angiogenesis, | 10 |
| abstract_inverted_index.transfection, | 72 |
| abstract_inverted_index.COX2-dependent | 205 |
| abstract_inverted_index.differentiated | 157 |
| abstract_inverted_index.Cyclooxygenase-2 | 0 |
| abstract_inverted_index.tumor-associated | 3 |
| abstract_inverted_index.COX2/MMP9-dependent | 163 |
| abstract_inverted_index.immunohistochemical | 48 |
| abstract_inverted_index.metalloproteinase-9 | 209 |
| cited_by_percentile_year.max | 99 |
| cited_by_percentile_year.min | 98 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 12 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.5400000214576721 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.96615188 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |