Cell Surface Expression of HIP, a Novel Heparin/Heparan Sulfate-binding Protein, of Human Uterine Epithelial Cells and Cell Lines

Rohde, Larry H.; Julian, JoAnne; Babaknia, A.; Carson, Daniel D.

doi:10.1074/jbc.271.20.11824

Cited by 51 publications

(82 citation statements)

References 35 publications

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“…In any case, HA-Hep is substantially enriched for anticoagulant activity and with regard to affinity for AT-III-Sepharose. Cell surface-expressed HIP has been suggested to be involved in Hep͞HS-dependent cell-cell or cell-extracellular matrix interactions (7,8). Results of the current study suggest another possible function of HIP, namely, modulation of blood coagulation activities.…”

Section: Discussionmentioning

confidence: 55%

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A heparin-binding synthetic peptide of heparin/heparan sulfateinteracting protein modulates blood coagulation activities

Liu¹,

Zhou²,

Höök³

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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We have previously identified and characterized a heparin-binding cell surface protein (heparin͞heparan sulfate-interacting protein, or HIP) present on epithelial and endothelial cells. A synthetic peptide mimicking a heparinbinding domain of HIP is now shown to bind a small subset of heparin molecules with high affinity and, therefore, presumably recognizes a specific structural motif in the heparin molecule. Further analyses revealed that the heparin molecules exhibiting a high affinity for the HIP peptide also show an extremely high affinity for antithrombin III (AT-III), a cofactor required for heparin's anticoagulant activity. The HIP peptide was shown to compete with AT-III for binding to heparin and to neutralize the anticoagulant activity of heparin in blood plasma assays. Furthermore, the heparin subfraction that binds to the HIP peptide with high affinity exhibits an extremely high anticoagulant activity. We conclude that although the HIP peptide shows no sequence similarity with AT-III, the two proteins recognize the same or similar structural motifs in heparin.

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Section: Discussionmentioning

confidence: 55%

“…HIP has been identified in human uterine epithelia and a variety of other human epithelial and endothelial cells (7,8). Analysis of the predicted amino acid sequence of HIP revealed a putative Hep͞HS-binding motif.…”

mentioning

confidence: 99%

A heparin-binding synthetic peptide of heparin/heparan sulfateinteracting protein modulates blood coagulation activities

Liu¹,

Zhou²,

Höök³

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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“…Collectively, these data indicated that secreted HS from different cell types was insensitive to heparanase digestion. HIP is a recently described cell surface HP/HS-binding protein (25,26) and contains a peptide motif that is capable of discriminating between secreted, cell surface, and ECM forms of HS. 2 Therefore, it was considered that heparanase and HIP peptide might recognize similar motifs in HS.…”

Section: Resultsmentioning

confidence: 99%

“…2 HIP is a novel protein found on the cell surface and is expressed in a cell type-specific fashion (25,26). The intact protein binds HP with high affinity (25,26). Additional studies have demonstrated that HIP peptide recognizes a subset of HP and HS (49).…”

Section: Discussionmentioning

confidence: 99%

“…secreted or associated with subendothelial ECM, are targets of heparanase action. Moreover, we have determined whether the HS motifs recognized by heparanase are the same as those recognized by a peptide motif of the recently discovered cell surface HS-binding protein, HIP (25,26). 2 HIP is a novel protein found on the cell surface and is expressed in a cell type-specific fashion (25,26).…”

Section: Discussionmentioning

confidence: 99%

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Heparanase and a Synthetic Peptide of Heparan Sulfate-interacting Protein Recognize Common Sites on Cell Surface and Extracellular Matrix Heparan Sulfate

Marchetti¹,

Liu²,

Spohn³

et al. 1997

Journal of Biological Chemistry

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Metastasis occurs via a sequential and complex series of interactions between tumor cells and normal host cells and tissues (1, 2). During the formation of metastases, migrating cells are confronted by natural tissue barriers, such as connective tissue stroma and basal lamina (2, 3). The ability of malignant cells to penetrate these barriers depends upon the presence of enzymes capable of degrading extracellular matrix (ECM) 1 components (1-5). For these reasons, considerable effort has been focused on the study of tissue-degradative enzymes produced and secreted by metastatic tumor cells as well as normal cells of the tissue being invaded.Important ECM targets for degradation by invading melanoma cells are the heparan sulfate (HS) chains found on proteoglycans (3, 6, 7). HS are highly negatively charged linear polysaccharides consisting of alternating residues of uronic acids and glucosamine. Proteins containing one or more covalently attached HS chains are called HS proteoglycans (HSPGs). The dynamic role of HSPGs in biology has become increasingly apparent (8 -23). As a result of characterizing heparin (HP) and HS binding sites related to the initial attachment of trophoblast cells to uterine epithelial cells of murine and human origin, we recently reported the cell surface expression and molecular cloning of a novel HP/HS-interacting protein (HIP) of human epithelial and endothelial cells (24 -26). HIP not only recognizes HS and HP in a highly specific fashion, but it also binds a subset of HP and forms of HS enriched at cell surfaces and in ECM. In contrast, HIP does not bind intracellular or secreted forms of HS. Furthermore, HIP also appears to bind the anticoagulantly active species of HP efficiently and with high affinity. 2 HP octasaccharides, but not hexasaccharides, are large enough to bind HIP with high affinity. Thus, HIP appears to recognize a motif that at least overlaps the anticoagulant motif in HP and HS chains.In light of the above findings, activities that mediate HSPG degradation are expected to have significant regulatory consequences. Indeed, HSPG catabolism is observed in inflammation, wound repair, diabetes, and cancer metastasis, suggesting that enzymes that degrade the HS chains play important roles in pathologic processes (3, 4). Furthermore, malignant cells are capable of modulating cellular interactions with HSPGs by producing and releasing a HS-degrading enzyme, heparanase (3,7,27,28). Recently, we reported that purified, high M r subpopulations of cell surface HS were more sensitive to heparanase action than secreted HS (29). In the present study, we have investigated the relationship between tumor (melanoma) heparanase activity and HIP binding in HS subpopulations whether on the cell surface, secreted, or deposited in the ECM. By use of sensitive heparanase assays that separate

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Specific degradation of subendothelial matrix proteoglycans by brain-metastatic melanoma and brain endothelial cell heparanases

Marchetti

1997

J. Cell. Physiol.

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One of the many features of the malignant phenotype, in vitro and in vivo, is elevated heparanase production and activity. Using in vitro model systems, we examined the capacity of murine (B16B15b) and human (70W) brain-metastatic melanoma cells to degrade the subendothelial matrix produced by endothelial cell monolayer cultures. B16B15b and 70W melanoma cells solubilized sulfated matrix proteoglycans at levels significantly higher than their parental lines (B16F1, MeWo). Sulfated matrix proteoglycans were rich in heparan sulfate (HSPGs), with minor amounts of chondroitin and dermatan sulfates. When matrix HSPGs were treated with pronase and alkaline borohydride to cleave the core proteins, the resulting glycosaminoglycan chains (GAGs) had an estimated M(r) of approximately 2.7 x 10(4) Da, with a minor subpopulation possessing an M(r) of approximately 4.5 x 10(4) Da. After their incubation with brain-metastatic melanoma cells, new HS fragments with lower M(r) estimated at approximately 9 x 10(3) Da were detected. This confirms action in these cells of heparanase, which is capable of cleaving GAGs at specific intrachain sites and releasing fragments of a relatively high M(r). The pattern of HSPG degradation by brain-metastatic melanoma cells differed from that of less metastatic parental cells or cells metastatic to organs other than the brain. Moreover, supraadditive levels of heparanase activity were found when brain endothelial cells were coin-cubated with brain-metastatic melanoma cells in equicellular amounts. Cooperative interactions between heparanases from tumor and endothelial sources in the invasion process are suggested and their potential mechanisms discussed.

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Cell Surface Expression of HIP, a Novel Heparin/Heparan Sulfate-binding Protein, of Human Uterine Epithelial Cells and Cell Lines

Cited by 51 publications

References 35 publications

A heparin-binding synthetic peptide of heparin/heparan sulfateinteracting protein modulates blood coagulation activities

A heparin-binding synthetic peptide of heparin/heparan sulfateinteracting protein modulates blood coagulation activities

Heparanase and a Synthetic Peptide of Heparan Sulfate-interacting Protein Recognize Common Sites on Cell Surface and Extracellular Matrix Heparan Sulfate

Specific degradation of subendothelial matrix proteoglycans by brain-metastatic melanoma and brain endothelial cell heparanases

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