Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.2.2.7 (heparinase)
 1,270 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glycosaminoglycans have been characterized from a normal human breast cell line (HBL-100) and two different cell lines from human breast carcinoma (MDA-MB-231 and MCF-7). The glycosaminoglycans were labeled by exposure of cell cultures to [3H]glucosamine and [35S]sulfate and then isolated from both spent media and cells by pronase digestion and cetylpyridinium chloride fractionation. They were further characterized by (a) hexosamine composition, (b) controlled-pore glass exclusion chromatography, (c) reactivity with specific enzymes (hyaluronidase chondroitinase, heparitinase, and heparinase), (d) nitrous acid degradation, and (e) DEAD-Sephadex chromatography. The results indicate that the HBL-100 line synthesizes mainly hyaluronic acid, most of which is secreted into the medium. Chondroitin sulfate and heparan sulfate are the predominant glycosaminoglycans synthesized by the cancer lines; both are found mainly in the spent medium, but the hyaluronic acid synthesized by the MDA-MB-231 line remains cell associated. The cell-associated heparan sulfate had a molecular weight in excess of 13,000 and may contain linkages susceptible to testicular hyaluronidase. The MCF-7 cells produce significantly lower amounts of glycosaminoglycans than do the other two lines.
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PMID:Glycosaminoglycans of normal and malignant cultured human mammary cells. 42 76

The human breast cancer cell lines MCF-7 and MDA-MB-231 differ in their responsiveness to fibroblast growth factor-2 (FGF-2). This growth factor stimulates proliferation in well-differentiated MCF-7 cells, whereas the less well-differentiated MDA-MB-231 cells are insensitive to this molecule. To investigate the potential regulation of FGF-2 mitogenic activity by heparan sulfate proteoglycans (HSPG), we have treated human breast cancer cells by glycosaminoglycan degrading enzymes or a metabolic inhibitor of proteoglycan sulfation: sodium chlorate. The interaction between FGF-2 and proteoglycans was assayed by examining the binding of 125I-FGF-2 to breast cancer cell cultures as well as to cationic membranes loaded with HSPG. Using MCF-7 cells, we showed that heparinase treatment inhibited FGF-2 binding to HSPG and completely abolished FGF-2 induced growth; chlorate treatment of MCF-7 cells decreased FGF-2 binding to HSPG and cell responsiveness in a dose-dependent manner. This demonstrates a requirement of adequately sulfated HSPG for FGF-2 growth-promoting activity on MCF-7 cells. In highly invasive MDA-MB-231 cells which produce twice as much HSPG as MCF-7 cells and which are not normally responsive to exogenously added FGF-2, chlorate treatment decreased FGF-2 binding to HSPG and induced FGF-2 mitogenic effect. This chlorate effect was dose dependent and observed at concentrations of 10-30 mM; higher chlorate concentrations completely abolished the FGF-2 effect. This shows that the HSPG level of sulfation can also negatively regulate the biological activity of FGF-2. Taken together, these results demonstrate a crucial role for HSPG in both positive and negative control of FGF-2 mitogenic activity in breast cancer cell proliferation.
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PMID:Heparan sulfate proteoglycans play a dual role in regulating fibroblast growth factor-2 mitogenic activity in human breast cancer cells. 898 23

We previously demonstrated that lactoferrin increases breast cell sensitivity to natural killer cell cytotoxicity whereas haematopoietic cells are unaffected by lactoferrin. It has been described that lactoferrin binds to various glycosaminoglycans. Compared to haematopoietic cells, breast cancer cells and particularly the breast cell line MDA-MB-231, possess a high level of proteoglycans. Scatchard analysis of 125I-lactoferrin binding to MDA-MB-231 cells revealed the presence of two classes of binding sites: a low affinity site with a Kd of about 700 nM and 3.9 x 10(6) sites and a higher affinity class with a Kd of 45 nM and 2.9 x 10(5) sites per cell. To investigate the potential regulation of lactoferrin activity by proteoglycans expressed on the MDA-MB-231 cells, we treated these cells with glycosaminoglycan-degrading enzymes or sodium chlorate, a metabolic inhibitor of proteoglycan sulphation. We showed that chondroitinase treatment has no effect, while heparinase or chlorate treatment significantly reduces both the binding of lactoferrin to cell surface sulphated molecules such as heparan sulphate proteoglycans (HSPG) and the affinity of lactoferrin for the higher affinity binding sites. The modulation of the lactoferrin binding was correlated with a decrease in lactoferrin activities on both MDA-MB-231 cell sensitisation to lysis and proliferation. Taken together, these results suggest that the presence of adequately sulphated molecules, in particular HSPG, is important for lactoferrin interaction and activity on the breast cancer cells MDA-MB-231.
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PMID:Role of heparan sulphate proteoglycans in the regulation of human lactoferrin binding and activity in the MDA-MB-231 breast cancer cell line. 993 Jun 59