Anti-tumor activities of chondroitinase AC and chondroitinase B: inhibition of angiogenesis, proliferation and invasion

Denholm, Elizabeth M.; Lin, Yongqing; Silver, Paul J.

doi:10.1016/s0014-2999(01)00884-6

Cited by 85 publications

(62 citation statements)

References 20 publications

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“…Cell surface CS/DS-PGs on human metastatic breast cancer cell lines have been suggested as receptors for P-selectin (Monzavi-Karbassi et al 2007). Furthermore, removal of CS/DS chains by chondroitinase B has been shown to inhibit endothelial and melanoma proliferation and invasion (Denholm et al 2001). DS-epi1 has been found upregulated in almost all cancers examined (Nakao et al 2000).…”

Section: Dermatan Sulfate and Cancermentioning

confidence: 99%

Iduronic Acid in Chondroitin/Dermatan Sulfate

Malmström

Bartolini

Thelin

et al. 2012

J Histochem Cytochem.

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The ability of chondroitin/dermatan sulfate (CS/DS) to convey biological information is enriched by the presence of iduronic acid. DS-epimerases 1 and 2 (DS-epi1 and 2), in conjunction with DS-4-O-sulfotransferase 1, are the enzymes responsible for iduronic acid biosynthesis and will be the major focus of this review. CS/DS proteoglycans (CS/DS-PGs) are ubiquitously found in connective tissues, basement membranes, and cell surfaces or are stored intracellularly. Such wide distribution reflects the variety of biological roles in which they are involved, from extracellular matrix organization to regulation of processes such as proliferation, migration, adhesion, and differentiation. They play roles in inflammation, angiogenesis, coagulation, immunity, and wound healing. Such versatility is achieved thanks to their variable composition, both in terms of protein core and the fine structure of the CS/DS chains. Excellent reviews have been published on the collective and individual functions of each CS/DS-PG. This short review presents the biosynthesis and functions of iduronic acid-containing structures, also as revealed by the analysis of the DS-epi1- and 2-deficient mouse models.

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Section: Dermatan Sulfate and Cancermentioning

confidence: 99%

Iduronic Acid in Chondroitin/Dermatan Sulfate

Malmström

Bartolini

Thelin

et al. 2012

J Histochem Cytochem.

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“…14) Gelatinase and collagenase activities were quantitated using a gelatinase/collagenase assay kit. Each sample was incubated with 100 mg/ml gelatin fluorescein conjugate (DQ gelatin) substrate and 0.2 U/ml Clostridium collagenase for 24 h at room temperature in 96-well plates.…”

Section: Antimentioning

confidence: 99%

Anti-angiogenic and Anti-tumor Activities of 2'-Hydroxy-4'-methoxychalcone

Lee

Lim

Shin

et al. 2006

Biological & Pharmaceutical Bulletin

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In the present study, we evaluated the in vitro and in vivo anti-angiogenic and anti-tumor activities of 2-hydroxy-4-methoxychalcone (HMC). HMC decreased angiogenesis in both chick embryos in the chorioallantoic membrane assay and basic fibroblast growth factor (bFGF)-induced vessel formation in the mouse Matrigel plug assay. This compound also reduced the proliferation of calf pulmonary arterial endothelial cells and was found to possess relatively weak gelatinase/collagenase inhibitory activity in vitro. HMC, when administered subcutaneously at the dose of 30 mg/kg for 20 d to mice implanted with murine Lewis lung carcinoma, caused a significant inhibition of tumor volume by 27.2%. Intraperitoneal (i.p.) treatment at the same dosage for 10 d to ICR mice bearing sarcoma 180 caused a significant suppression in tumor weight by 33.7%. Taken together, out data demonstrate that the anti-angiogenic activities of HMC might be due to anti-proliferative activity under inhibition of the induction of COX-2 enzyme. Furthermore, the results suggest that the potent anti-angiogenic activity of HMC seems to be the possible mechanism of action in these animal models of solid tumors.

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“…CS has been found in large amounts in melanomas (1,2) and other types of cancer (3,4). CS seems to play an important role in tumor growth, given that the treatment of tumors with chondroitinase AC results in reduced tumor growth and invasion (5) and CS-targeting liposomes have been used to target drugs to metastases in mice (6).…”

Section: Introductionmentioning

confidence: 99%

Chondroitin Sulfate E Fragments Enhance CD44 Cleavage and CD44-Dependent Motility in Tumor Cells

et al. 2008

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During tumor cell invasion, certain extracellular matrix (ECM) components such as hyaluronan (HA) are degraded into small oligosaccharides, which are detected in patients. We previously reported that such HA oligosaccharides induce the proteolytic cleavage of an ECM-binding molecule CD44 from tumor cells and promote tumor cell migration in a CD44-dependent manner. Here, we report that chondroitin sulfate E (CSE), another component of the tumor ECM, strongly enhances CD44 cleavage and tumor cell motility when degraded into oligosaccharides. CSE and its degradation products were detected in pancreatic ductal adenocarcinoma. In CD44-expressing pancreatic tumor cells, degraded forms of CSE but not intact CSE enhanced CD44 cleavage; enzymatic digestion of such low-molecular weight CSE (LMW-CSE) abrogated this enhancement. Among the LMW-CSE preparations examined, 3-kDa CSE most potently induced CD44 cleavage. Nuclear magnetic resonance analysis showed that the 3-kDa-CSE bound to CD44, and that blocking such binding abrogated the CD44 cleavage induction. LMW-CSE also induced prominent filopodia formation and cytoskeletal changes in tumor cells; these effects were also abrogated by blocking the LMW-CSE binding to CD44. Chemically synthesized CSE hexasaccharides also enhanced the CD44 cleavage and tumor cell motility in a CD44-dependent manner. We conclude that the degraded forms of CSE modulate cell adhesion and migration by interacting with tumor-cell CD44, suggesting that the degradation products of tumor-associated ECMs that interact with CD44 play a significant role in CD44-mediated tumor progression. [Cancer Res 2008;68(17):7191-9]

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Anti-tumor activities of chondroitinase AC and chondroitinase B: inhibition of angiogenesis, proliferation and invasion

Cited by 85 publications

References 20 publications

Iduronic Acid in Chondroitin/Dermatan Sulfate

Iduronic Acid in Chondroitin/Dermatan Sulfate

Anti-angiogenic and Anti-tumor Activities of 2'-Hydroxy-4'-methoxychalcone

Chondroitin Sulfate E Fragments Enhance CD44 Cleavage and CD44-Dependent Motility in Tumor Cells

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