Anti‐angiogenic properties of ADAMTS‐4 <i>in vitro</i>

Hsu, Yi-Ping; Staton, Carolyn A.; Cross, Neil; Buttle, David J.

doi:10.1111/j.1365-2613.2011.00802.x

Cited by 43 publications

(45 citation statements)

References 42 publications

(63 reference statements)

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“…However, more recently ADAMTS-4 has been shown to have anti-angiogenic activities in vitro including binding to VEGF and inhibiting VEGF receptor 2 phosphorylation in human dermal microvascular ECs (10).…”

Section: Discussionmentioning

confidence: 99%

“…The presence of ADAMTS-1, -4 and -5 in these HCC cell lines may indicate a role in tumour development and progression as they degrade extracellular matrix large aggregating proteoglycans (23). Conversely, ADAMTS-1, -4 and -5 may inhibit angiogenesis thus inhibiting tumour growth (9)(10)(11).…”

Section: Discussionmentioning

confidence: 99%

“…However ADAMTS-1, -4 and -5 have recently been shown to also have, at least in a certain context, anti-angiogenic properties (9)(10)(11). The anti-angiogenic activity of ADAMTS-1 has been mapped to the three TSRs in the C-terminus of this protein; however the spacer domain must also be present to elicit an anti-tumour response (12).…”

Section: Introductionmentioning

confidence: 99%

“…The first TSR of ADAMTS-5 has also been shown to function as an angiogenesis inhibitor in vitro (5). The regions responsible for the in vitro anti-angiogenic properties of ADAMTS-4 require confirmation but are thought to include the central TSR and cysteine-rich domain (10). Conversely, ADAMTS-4 can also function to advance tumour progression; however its specific role has not yet been determined (13).…”

Section: Introductionmentioning

confidence: 99%

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Expression of ADAMTS-1, ADAMTS-4, ADAMTS-5 and TIMP3 by hepatocellular carcinoma cell lines

Turner

Mangnall

Bird

et al. 2012

International Journal of Oncology

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Abstract.Little is known about the expression or role of ADAMTS-1, -4 and -5 and their endogenous inhibitor TIMP3 in the liver in physiological and pathological conditions. Their expression was, therefore, investigated in the hepatocellular carcinoma cell lines HepG2 and HuH-7 using qRT-PCR and western blotting, and their cellular localisation by immunocytochemistry. Cytokine treatments were used to assess mRNA and protein modulation. ADAMTS-1, -4, -5 and TIMP3 mRNA and protein were detected in both HepG2 and HuH-7 cells. IL-1β and IL-6 treatments significantly modulated ADAMTS-1 mRNA expression and IL-1β treatment ADAMTS-4 mRNA expression in HepG2 cells. Modulations of mRNA by ≥5-fold did not translate to increased protein expression. This study showed that ADAMTS-1, -4, -5 and TIMP3 were expressed at differential levels in hepatocellular carcinoma cell lines. The pro-inflammatory cytokines IL-1β, TNF-α or IL-6 induced changes in mRNA expression, although these did not translate to the protein level. IntroductionHepatocellular carcinoma (HCC) is the most common primary malignant tumour occurring in the liver which accounts for 80-90% of all primary liver cancers (1). In many cases, the neoplastic transformation of hepatocytes results from accumulation of genetic changes during enhanced cell proliferation in the injured liver in response to paracrine growth factor and cytokine stimulation (2). HCCs have a considerable capacity for vascular invasion, with metastasis and recurrence being the major factors associated with the poor prognosis of HCC (3).Proteolytic modification of cell surface proteins and extracellular matrix (ECM) plays a pivotal role in cancer development and metastasis. Proteolytic enzymes are involved in several processes, at the cellular and organism level, which are dysregulated in cancer, e.g. cell adhesion and migration, cell invasion and angiogenesis. In particular, they mediate tumour invasion at several stages, e.g. detachment of cells from the primary tumour, crossing vessel walls and extravasation into target organs. This involves attachment of oncogenically transformed cells to the ECM followed by its degradation and movement of invading cells through the damaged ECM (4,5).Expression and activity of several classes of proteolytic enzymes have been shown to be modified in cancer, including recently discovered a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs). There are 19 ADAMTSs which can be involved in pathological processes such as ECM breakdown and angiogenesis (6). They consist of several domains: the prodomain, metalloproteinase domain, disintegrin-like domain, cysteine-rich domain, thrombospondin type-I repeats (TSRs) and a spacer domain. Several ADAMTSs also contain an additional unique domain(s). They are synthesised as zymogens and after proteolytic processing at the N-terminus to remove the signal sequence and prodomain, they are secreted from cells. For most ADAMTSs this is an important step in their activation. ADAMTSs may also undergo C-terminal proc...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Expression of ADAMTS-1, ADAMTS-4, ADAMTS-5 and TIMP3 by hepatocellular carcinoma cell lines

Turner

Mangnall

Bird

et al. 2012

International Journal of Oncology

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“…The function of ADAMTS15 in the colon is not known; however, its broad and high expression level is concordant with its proposed role in colorectal cancer as a tumor suppressor gene. Although the mechanism(s) underlying ADAMTS15's tumor suppression capabilities are unknown, the anti-angiogenic nature of several other ADAMTS proteoglycanases has been characterized, including ADAMTS15's evolutionary partner ADAMTS8 (47)(48)(49)(50). In addition, ADAMTS9 has recently been identified as a putative tumor suppressor gene through its anti-angiogenic properties in esophageal and nasopharyngeal carcinoma (51).…”

mentioning

confidence: 99%

Biosynthesis and Expression of a Disintegrin-like and Metalloproteinase Domain with Thrombospondin-1 Repeats-15

Dancevic¹,

Fraser²,

Smith

et al. 2013

Journal of Biological Chemistry

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Background: ADAMTS proteoglycanases show proteolytic activity toward versican and other proteoglycans. Results: ADAMTS15, which cleaves versican, is expressed during early cardiac development and during musculoskeletal development. Conclusion: With unique and overlapping biological properties, ADAMTS15 is likely to have cooperative roles with other members of the ADAMTS proteoglycanase clade. Significance: Versican cleavage has profound effects on developmental morphogenesis and regulates cancer cell behavior.

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Single‐nucleotide polymorphisms in the coding region of a disintegrin and metalloproteinase with thrombospondin motifs 4 and hepatocellular carcinoma: A retrospective case‐control study

Wang

Tang

et al. 2019

Cancer Medicine

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Previous studies have shown that single‐nucleotide polymorphisms (SNPs) of a disintegrin and metalloproteinase with thrombospondin type 1 motif 4 (ADAMTS4) may involve in the pathogenesis of some diseases. However, it is not clear whether they are associated with hepatocellular carcinoma (HCC). A hospital‐based case‐control study, including 862 cases with HCC and 1120 controls, was conducted to assess the effects of 258 SNPs in the coding regions of ADAMTS4 on HCC risk and prognosis. We found that six SNPs in ADAMTS4 were differential distribution between cases and controls via the primary screening analyses; however, only rs538321148 and rs1014509103 polymorphisms were further identified to modify the risk of HCC (odds ratio: 2.73 and 2.95; 95% confidence interval, 2.28‐3.29 and 2.43‐3.58; P‐value, 5.73 × 10−27 and 1.36 × 10−27, respectively). Significant interaction between these two SNPs and two known causes of hepatitis B virus and aflatoxin B1 were also observed. Furthermore, rs538321148 and rs1014509103 polymorphisms were associated not only with clinicopathological features of tumor such as tumor stage and grade, microvessel density, and vessel metastasis, but with poor overall survival. Additionally, these SNPs significantly downregulated ADATMS4 expression in tumor tissues. These data suggest that SNPs in the coding region of ADAMTS4, such as rs538321148 and rs1014509103, may be potential biomarkers for predicting HCC risk and prognosis.

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Anti‐angiogenic properties of ADAMTS‐4 in vitro

Cited by 43 publications

References 42 publications

Expression of ADAMTS-1, ADAMTS-4, ADAMTS-5 and TIMP3 by hepatocellular carcinoma cell lines

Expression of ADAMTS-1, ADAMTS-4, ADAMTS-5 and TIMP3 by hepatocellular carcinoma cell lines

Biosynthesis and Expression of a Disintegrin-like and Metalloproteinase Domain with Thrombospondin-1 Repeats-15

Single‐nucleotide polymorphisms in the coding region of a disintegrin and metalloproteinase with thrombospondin motifs 4 and hepatocellular carcinoma: A retrospective case‐control study

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