Abstract:
:To explore the mechanisms through which hypoxic tumor microenvironment (TME) modulates the transition of tumor-associated macrophages (TAMs). The migration ability of RAW264.7 macrophages was determined by transwell assay. Flow cytometric, western blot and immunofluorescence analyses of CD206 further validated the M2 polarization of macrophages. Immunofluorescence, western blot and qRT-PCR were performed to detect the expression of neuropilin-1 (Nrp-1) and carbonic anhydrase IX (CAIX). An intermittent hypobaric hypoxia (IH) animal model was established to evaluate the role of hypoxia in activating M2-like TAMs in vivo. We also used immunohistochemistry to analyze the association between CAIX, CD163+ macrophages and Nrp-1 in a series of 72 human cervical cancer specimens. We found that the hypoxic cervical TME educated the recruited macrophages to transform into the M2 phenotype. Nrp-1 expression was significantly increased in hypoxia-primed cervical cancer cells. Blocking Nrp-1 expression prevented hypoxic cells from recruiting and polarizing macrophages towards the M2 phenotype. Hypoxia exposure significantly increased the expression of Nrp-1 as well as the infiltration of macrophages in vivo. Consistently, immunochemical staining in serial tissue sections of cervical cancer revealed upregulated levels of Nrp-1 in CAIX-positive hypoxic regions along with a concurrent significant elevation of M2 macrophages. Nrp-1 and M2-like TAMs were related to the malignant properties of cervical cancer, such as the FIGO stage and lymph node metastasis. Nrp-1 plays critical roles in hypoxic TME-induced activation and pro-tumoral effects of TAMs in cervical cancer. Interfering with Nrp-1 may be a potential therapeutic strategy in treating cervical cancer.
journal_name
Mol Carcinogjournal_title
Molecular carcinogenesisauthors
Chen XJ,Wu S,Yan RM,Fan LS,Yu L,Zhang YM,Wei WF,Zhou CF,Wu XG,Zhong M,Yu YH,Liang L,Wang Wdoi
10.1002/mc.22936subject
Has Abstractpub_date
2019-03-01 00:00:00pages
388-397issue
3eissn
0899-1987issn
1098-2744journal_volume
58pub_type
杂志文章abstract::Tumor-associated stromal cells are dynamic characters that endorse the carcinogenic process in a multitude of ways. The tumor microenvironment plays a crucial role throughout the tumor progression, which includes initiation, growth, invasion, and metastasis. The tumor microenvironment consists of cellular and non-cell...
journal_title:Molecular carcinogenesis
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abstract::microRNAs (miRNA) silence target genes through Watson-Crick based binding to the 3'untranslated regions (3'UTR). Thus, polymorphisms in the miRNA-binding sites may disrupt this process and play a potential role in cancer pathogenesis. Integrins have been implicated in the genesis and development of many tumors. This s...
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journal_title:Molecular carcinogenesis
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journal_title:Molecular carcinogenesis
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更新日期:2018-09-01 00:00:00
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journal_title:Molecular carcinogenesis
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journal_title:Molecular carcinogenesis
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journal_title:Molecular carcinogenesis
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更新日期:2014-01-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2001-12-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(199710)20:2<204::aid-mc7>3
更新日期:1997-10-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940050112
更新日期:1992-01-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940080205
更新日期:1993-01-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.23246
更新日期:2020-10-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22290
更新日期:2016-04-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:
更新日期:2000-12-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2744(199607)16:3<149::AID-MC5>3
更新日期:1996-07-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
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更新日期:2014-02-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22379
更新日期:2016-09-01 00:00:00
abstract::Prostate cancer (PCa) patients' mortality is mainly attributed to complications caused by metastasis of the tumor cells to organs critical for survival, such as bone. We hypothesized that PCa cell-bone interactions would promote paracrine signaling. A panel of PCa cell lines were cocultured with hydroxyapatite ([HA]; ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.23019
更新日期:2019-08-01 00:00:00
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journal_title:Molecular carcinogenesis
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doi:10.1002/mc.20648
更新日期:2010-08-01 00:00:00
abstract::Numerous studies have shown that aberrant microRNA (miRNA) expression is associated with the development and progression of various types of human cancer and serum miRNAs are potential biomarkers. This study examined whether some commonly deregulated miRNAs in hepatocellular carcinoma (HCC) are presented in serum of p...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20712
更新日期:2011-02-01 00:00:00
abstract::Sel-1-like (SEL1L) is a putative tumor suppressor gene that is significantly downregulated in human pancreatic ductal adenocarcinoma (PDA). The mechanism of the downregulation is unclear. Here, we investigated whether aberrantly upregulated microRNAs (miRNAs) repressed the expression of SEL1L. From reported miRNA micr...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22023
更新日期:2014-09-01 00:00:00
abstract::The majority of human neoplasms have aberrations in the retinoblastoma pathway due to hyperactivation of cyclin-dependent kinases (CDK). Based on this observation, novel small molecules, such as flavopiridol and UCN-01, are being developed and are currently being tested in the clinic. Efforts to develop CDK modulators...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.10114
更新日期:2003-04-01 00:00:00
abstract::Although fibroblast growth factor (FGF) signals are strongly associated with malignancy, limited information is available regarding the role of the FGF9 signal in colorectal cancer (CRC). In this study, we investigated the frequency of FGF9 amplification in CRC clinical specimens and the association between the FGF9 g...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22476
更新日期:2017-01-01 00:00:00
abstract::Prostate cancer (PCA) is the second most malignancy in American men. Advanced stage PCA cells possess unlimited replication potential as well as resistance to apoptosis. Therefore, targeting survival mechanisms and activating apoptotic machinery in PCA cells using nontoxic phytochemicals is suggested as an attractive ...
journal_title:Molecular carcinogenesis
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doi:10.1002/mc.20670
更新日期:2010-10-01 00:00:00