ADAMTS Expression in Colorectal Cancer

Filou, Serafoula; Korpetinou, Aggeliki; Kyriakopoulou, Dora; Bounias, Dimitrios; Stavropoulos, M.; Ravazoula, Panagiota; Papachristou, Dionysios J.; Theocharis, Achilleas D.; Vynios, Demitrios H.

doi:10.1371/journal.pone.0121209

Cited by 29 publications

(25 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this context, ADAMTS family, as a relatively new group of ECM metalloproteinases, have become one of the promising foci in the recent studies on cancer. To date, many clinical studies regarding the relationship between AD-AMTS proteases and various types of cancer have been reported (7)(8)(9)(10). However, there are limited data on the role of ADAMTSs in gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

Differentially regulated ADAMTS1, 8, and 18 in gastric adenocarcinoma

Kılıç¹,

Aynekin²,

Kara³

et al. 2017

BLL

View full text Add to dashboard Cite

OBJECTIVE: The aim is to investigate the expression status of ADAMTS1,8, and 18 proteases in gastric cancer (GC) and lymphatic metastasis. BACKGROUND: A disintegrin and metalloprotease with thrombospondin motifs (ADAMTS) is a new protease family, and has important biological functions such as hemostasis, extracellular matrix remodeling and regulation of angiogenesis. METHODS: The immunostaining status of ADAMTS1,8, and 18 were investigated in formalin-fi xed paraffi nembedded samples of 25 patients who underwent curative resection for GC. RESULTS: The immune reactivity scores (IRS) of ADAMTS1, 8, and 18 were signifi cantly higher in the cancerous gastric tissue in comparison to non-cancerous gastric tissue (p < 0.001). In addition, IRS scores of these three ADAMTS proteases were higher in the metastatic lymph nodes compared with healthy lymph nodes (p < 0.001). The expression status of the three ADAMTSs in cancerous gastric tissue was correlated with stage of tumor. Additionally, ADAMTS1 expression and ADAMTS8 expression in cancerous gastric tissue were found to correlate with grade and tumor size, respectively. CONCLUSION: This study showed that ADAMTS1, 8, and 18 are highly expressed in GC and its nodal metastases, suggesting important roles of these proteases in carcinogenesis and lymphatic metastasis. The fi ndings from the present study indicate that these proteases may be promising candidates for novel and alternative treatments in GC (Tab. 3, Fig. 3, Ref. 27). Text in PDF www.elis.sk.

show abstract

Section: Discussionmentioning

confidence: 99%

Differentially regulated ADAMTS1, 8, and 18 in gastric adenocarcinoma

Kılıç¹,

Aynekin²,

Kara³

et al. 2017

BLL

View full text Add to dashboard Cite

show abstract

“…ADAMTS8, ADAMTS12 and AD-AMTS18) were frequently methylated and down-regulated in various carcinomas [29-31]. ADAMTS1, ADAMTS15 and ADAMTS20 are down-regulated in CRC progress [32-33]. It has also been shown that the promoters of ADAMTS1, ADAMTS5, ADAMTS9, ADAMTS12, ASDAMTS15 and ADAMTS18 are methylated in CRC, suggesting a decreased expression of the proteins in this state [29-31, 34].…”

Section: Discussionmentioning

confidence: 99%

ADAMTS9 is Silenced by Epigenetic Disruption in Colorectal Cancer and Inhibits Cell Growth and Metastasis by Regulating Akt/p53 Signaling

Chen

Tang

Feng

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: ADAMTS (disintegrin-like and metalloproteinase with thrombospondin motifs) proteins are extracellular zinc metalloproteinases that play an important role in extracellular matrix assembly and degradation, connective tissue structuring, angiogenesis, and cell migration. Multiple studies suggest that ADAMTS proteins (e.g. ADAMTS9) can act as tumor suppressors. In gastric, esophageal, and nasopharyngeal carcinomas ADAMTS9 is frequently down-regulated by promoter methylation. Whether ADAMTS9 can function as a tumor suppressor gene (TSG) in colorectal cancer is still unclear. Methods: We performed immunohistochemistry, RT-PCR, and qRT-PCR, to examine the expression of ADAMTS9 in colorectal cancer cell lines and primary colorectal cancer tissues. Methylation-specific PCR was also carried out to investigate the promoter methylation status of ADAMTS9. We also explored the functions of ADAMTS9 in colorectal cancer cell lines through in vitro experiments. Results: ADAMTS9 expression was down-requlated or silenced in 83.3% (5/6) of colorectal cancer cell lines, and frequently repressed in 65.6% (21/32) of colorectal cancer tissues. Down-regulation of ADAMTS9 was partially due to promoter methylation. Exogenous expression of ADAMTS9 in colorectal cancer cell lines inhibited cell proliferation and migration through the regulation of cell cycle and apoptosis. In addition, ADAMTS9 prevented the activation of Akt, and its downstream targets in colorectal cancer cell lines. Conclusion: Our findings suggest ADAMTS9 is a TSG in colorectal cancer.

show abstract

“…Emerging evidence has demonstrated that ADAMTS are deregulated in human cancer and implicated in tumor progression [8,13]. Meanwhile, somatic mutations of ADAMTS genes are associated with chemotherapy sensitivity and patients' survival [20,21].…”

Section: Differentially Expressed Adamts4 Predicts a Poor Prognosis Imentioning

confidence: 99%

“…Most of ADAMTSs include the following domain structure from the N-terminus to C-terminal: 1) a signal peptide directs ADAMTS to the secretory pathway; 2) a prodomain maintains enzyme latency; 3) a zinc binding metalloproteinase domain; 4) a disintegrin-like domain; 5) a central Thrombospondin Type 1 repeat (TSR); 6) a cysteine rich domain; 7) a spacer domain; 8) variable number of TSRs [6,7]. ADAMTSs are involved in diverse functions including matrix degradation, collagen maturation, blood coagulation, organogenesis, and inflammation [8,9]. However, the functions, mechanisms of activation, and substrates of most ADAMTS members remain largely unexplored [10].…”

Section: Introductionmentioning

confidence: 99%

“…However, the functions, mechanisms of activation, and substrates of most ADAMTS members remain largely unexplored [10]. In cancers, ADAMTSs can play both oncogenic and tumor-protective roles through regulating matrix-degradation, angiogenesis and metastasis [8,[11][12][13][14][15][16]. Moreover, ADAMTSs mutation is significantly associated with improved chemotherapy sensitivity and progression-free survival in ovarian cancer [17].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Chen

Luo

Zhou

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: ADAMTSs (A disintegrin and metalloprotease domains with thrombospondins motifs) are a family of extracellular proteases that have been related to both oncogenic and tumor-suppressive functions. The aim of the present study was to investigate: 1) the mutation, copy-number alterations, and expression profile of ADAMTSs in colorectal cancer and 2) whether ADAMTSs participate in colorectal cancer (CRC) progression and invasion. Methods: The mutation, copy-number alterations, and expression profile of ADAMTSs in CRC were analyzed in the TCGA cohort using cBioportal. ADAMTS4 expression in tumor tissues and cell lines were determined by immunostaining and real-time quantitative PCR. The role of ADAMTS-4 in CRC progression and the underlying mechanisms were studied by using short hairpin RNA-mediated knockdown of ADAMTS4. The effects of ADAMTS4 in cell proliferation and invasion were determined by clone formation assay and transwell migration assay, respectively. Macrophages were depleted by liposomal clodronate in immune-competent BALB/c mice and tumor growth was analyzed. Results: ADAMTS4 was differentially expressed in CRC and predicted a poor prognosis. Elevated ADAMTS4 expression was closely associated with larger tumor size, enhanced TNM stage, and a poor clinical outcome in patients with CRC. ADAMTS4 knockdown had no inhibitory implications on cell proliferation and invasion in vitro, but significantly attenuated tumor growth in vivo. Mechanistically, we revealed that ADAMTS4 was associated macrophages infiltration and polarization in the tumor microenvironment of CRC. Macrophage depletion largely abolished the promotive effect of ADAMTS4 on tumor growth in the immune competent BALB/c mice. Conclusion: ADAMTS4 seemed to be a promising prognostic indicator in CRC. The novel link between ADAMTS4 and macrophages mirrors the potential regulatory roles of ADAMTSs in the inflammatory microenvironment of cancers.

show abstract

ADAMTS Expression in Colorectal Cancer

Cited by 29 publications

References 35 publications

Differentially regulated ADAMTS1, 8, and 18 in gastric adenocarcinoma

Differentially regulated ADAMTS1, 8, and 18 in gastric adenocarcinoma

ADAMTS9 is Silenced by Epigenetic Disruption in Colorectal Cancer and Inhibits Cell Growth and Metastasis by Regulating Akt/p53 Signaling

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

Contact Info

Product

Resources

About