Promotion of Tumor Growth by ADAMTS4 in Colorectal Cancer: Focused on Macrophages

Chen, Jianjun; Luo, Yang; Zhou, Yong; Qin, Shao-Lan; Qiu, Yier; Cui, Ran; Yu, Minhao; Qin, Jun; Zhong, Ming

doi:10.1159/000489245

Cited by 27 publications

(21 citation statements)

References 25 publications

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“…ADAMTS4 is highly expressed in colon cancer and is associated with poor prognosis [ 27 ]. ADMATS4 was also found to be mutated in early-onset familial colorectal cancer [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Values for the mRNA Expression of the ADAMTS Family of Genes in Gastric Cancer

Liang

Zhu

Chen

et al. 2020

Journal of Oncology

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The “A Disintegrin and Metalloproteinase with Thrombospondin Motif” (ADAMTS) family of genes is involved in the occurrence and development of different cancers. However, the prognostic value of these genes in gastric cancer (GC) has not been revealed. The present study was thus conducted to determine the prognostic value for the ADAMTS family of genes in GC. First, we evaluated the mRNA expression levels of the ADAMTS family in GC patients using a GEPIA dataset. Thereafter, we determined the prognostic value of these genes by analyzing their mRNA level using the Kaplan–Meier Plotter database. The mRNA expression level of ADAMTS12 was randomly validated by qRT-PCR and meta-analysis while its coexpression genes were derived using Coexpedia. Finally, we performed Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses using the OmicShare Tools. Compared to normal tissues, expression of ADAMTS2 and 12 was significantly higher while that of ADAMTS1, 13, and 15 was significantly lower in GC tissues. According to the RNA-seq and gene chip data, the ADAMTS family (6, 7, 12, 15, and 18) of genes was closely related to the prognosis of GC, and their high expression levels were associated with poor prognosis and survival time. In addition, ADAMTS12 was highly expressed in 20 pairs of GC tissues based on RT-PCR (P=0.016) and meta-analysis (SMD: 0.73, 95% CI: 0.32–1.14, P<0.001). GO and KEGG pathway analyses indicated that the ADAMTS12 coexpressed genes were enriched in the pathways of extracellular matrix organization, extracellular matrix structural constituent, extracellular matrix, and protein digestion and absorption. Herein, we discovered the prognostic values and biological roles of the ADAMTS genes in GC.

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“…ADAMTS4 is highly expressed in colon cancer and is associated with poor prognosis [ 27 ]. ADMATS4 was also found to be mutated in early-onset familial colorectal cancer [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Values for the mRNA Expression of the ADAMTS Family of Genes in Gastric Cancer

Liang

Zhu

Chen

et al. 2020

Journal of Oncology

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“…These present results support the notion that ADAMTS4 is overexpressed in both CRC clinical specimens and CRC cell lines, which is consistent with previous studies. 20,21 The present study had special advantages. In the beginning, the evidence was complete and consolidated.…”

Section: Discussionmentioning

confidence: 93%

ADAMTS4 is upregulated in colorectal cancer and could be a useful prognostic indicator of colorectal cancer

Shang

Liu

et al. 2020

Rev. Assoc. Med. Bras.

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SUMMARY OBJECTIVE ADAMTS4 is a member of the ADAMTS4 family, which secretes proteinases. The mechanism of tumor metastasis may be correlated to its promotion of angiogenesis. It was determined whether ADAMTS4 participates in colorectal cancer progression. Methods The expression in clinical samples and CRC cell lines was investigated. Using immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and RT-PCR, the expression of ADAMTS4 was determined in colorectal tumors of different cancer stages and anatomic sites, and in three cell lines of different aggressiveness. Results The overexpression of ADAMTS4 was observed in tissue samples by IHC, and this was mainly located in the cytoplasm, as detected by FISH. The qRT-PCR and western blot analyses further supported the clinical sample findings. Conclusion The present data support the notion that the overexpression of ADAMTS4 in CRC might be useful as a non-invasive biomarker for detecting CRC in patients.

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“…By in silico protease mapping the proteases ADAMTS4, CMA1 and KLK4 were predicted to be increased in their activity in CCA, whereas CASP1 and KLK6 were predicted to be decreased. ADAMTS4 was reported to promote tumor growth in colorectal cancer and is associated with macrophage infiltration [32]. CMA1 is released by activated mast cells to degrade the ECM.…”

Section: Discussionmentioning

confidence: 99%

Bile and urine peptide marker profiles: access keys to molecular pathways and biological processes in cholangiocarcinoma

et al. 2020

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Background: Detection of cholangiocarcinoma (CCA) remains a diagnostic challenge. We established diagnostic peptide biomarkers in bile and urine based on capillary electrophoresis coupled to mass spectrometry (CE-MS) to detect both local and systemic changes during CCA progression. In a prospective cohort study we recently demonstrated that combined bile and urine proteome analysis could further improve diagnostic accuracy of CCA diagnosis in patients with unknown biliary strictures. As a continuation of these investigations, the aim of the present study was to investigate the pathophysiological mechanisms behind the molecular determinants reflected by bile and urine peptide biomarkers.Methods: Protease mapping and gene ontology cluster analysis were performed for the previously defined CE-MS based biomarkers in bile and urine. For that purpose, bile and urine peptide profiles (from samples both collected at the date of endoscopy) were investigated from a representative cohort of patients with benign (n = 76) or CCA-associated (n = 52) biliary strictures (verified during clinical follow-up). This was supplemented with a literature search for the association of the individual biomarkers included in the proteomic patterns with CCA or cancer progression.Results: For most of the peptide markers, association to CCA has been described in literature. Protease mapping revealed ADAMTS4 activity in cleavage of both bile and urine CCA peptide biomarkers. Furthermore, increased chymase activity in bile points to mast cell activation at the tumor site. Gene ontology cluster analysis indicates cellular response to chemical stimuli and stress response as local and extracellular matrix reorganization by tissue destruction and repair as systemic events. The analysis further supports that the mapped proteases are drivers of local and systemic events. Conclusions: The study supports connection of the CCA-associated peptide biomarkers to the molecular pathophysiology and indicates an involvement in epithelial-to-mesenchymal transition, generation of cancer-associated fibroblasts and activation of residual immune cells. Proteases, extracellular matrix components, inflammatory cytokines, proangiogenic, growth and vasoactive factors released from the tumor microenvironment are drivers of systemic early events during CCA progression.

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Promotion of Tumor Growth by ADAMTS4 in Colorectal Cancer: Focused on Macrophages

Cited by 27 publications

References 25 publications

Prognostic Values for the mRNA Expression of the ADAMTS Family of Genes in Gastric Cancer

Prognostic Values for the mRNA Expression of the ADAMTS Family of Genes in Gastric Cancer

ADAMTS4 is upregulated in colorectal cancer and could be a useful prognostic indicator of colorectal cancer

Bile and urine peptide marker profiles: access keys to molecular pathways and biological processes in cholangiocarcinoma

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