Interactions of recombinant and platelet transforming growth factor-β1 precursor with the insulin-like growth factor II/mannose 6-phosphate receptor

Kovacina, Kristina S.; Steele-Perkins, George; Purchio, Anthony F.; Lioubin, Mario N.; Miyazono, Kohei; Heldin, Carl‐Henrik; Roth, Richard A.

doi:10.1016/0006-291x(89)91669-0

Cited by 128 publications

(65 citation statements)

References 29 publications

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“…DAB was used as a chromogen essentially as described above. In this case, the nucleii of of CCl 4 (Fig. 1).…”

Section: Methodsmentioning

confidence: 86%

“…3A). Eight hours after one injection of CCl 4 As a control for equiva-were studied using Northern blot analysis in freshly lent transfer and integrity of the samples, the blots were later probed isolated (0 days) and cultured FSCs (3, 6, and 12 days).…”

Section: Resultsmentioning

confidence: 99%

“…To induce acute liver injury, 42 rats followed by centrifugation for 20 minutes at 4000g. Nonspereceived a single, intraperitoneal dose of 150 mL of CCl 4 , cific binding was measured in the absence of antiserum. IGFdissolved in an equal volume of mineral oil, per 100 g body II/M6P receptor affinity purified from rat liver membrane weight.…”

Section: Methodsmentioning

confidence: 99%

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Insulin-like growth factor II/mannose 6-phosphate-receptor expression in liver and serum during acute CCl4 intoxication in the rat

Bleser¹

1996

Hepatology

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6 While the membrane form of the receptor min immunostaining. Between 48 and 72 hours, the liver plays a role in lysosomal enzyme targeting and the gradually regained its normal appearance. As shown by promotion of cell proliferation, the role of the soluble Western blotting, in vitro differentiated FSCs released receptor remains enigmatic. It has been suggested that soluble receptor in the medium. Northern blot analysis release of soluble receptor is a mechanism of receptor showed this release to be preceded by an increased re-turnover and degradation 7 as well as a means of moduceptor-mRNA expression, whereas immunostaining lating the activity of the receptor ligands present in showed an increase of intracellular receptor. In conclu-the extracellular space. 8 Recently, the age and tissue-specific pattern of soluble receptor release from rat tissue explants in culture Abbreviations: IGF-II/M6P, insulin-like growth factor-II/mannose 6-phosphate; TGF-b, transforming growth factor b; FSC, fat-storing cell; GBSS, Gey's was examined. 8 The highest release of receptor in adult

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“…DAB was used as a chromogen essentially as described above. In this case, the nucleii of of CCl 4 (Fig. 1).…”

Section: Methodsmentioning

confidence: 86%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Insulin-like growth factor II/mannose 6-phosphate-receptor expression in liver and serum during acute CCl4 intoxication in the rat

Bleser¹

1996

Hepatology

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“…Furthermore, L-TGF␤ is internalized and degraded in the lysosomes subsequent to its binding to the M6P/IGF-II receptor. 53 In addition, Monsigny et al showed that M6P 20 -BSA was endocytosed and rapidly degraded in monocytes or macrophages. 26 At present, we are studying this subject in isolated rat HSC in culture.…”

Section: Discussionmentioning

confidence: 99%

Albumin modified with mannose 6-phosphate: A potential carrier for selective delivery of antifibrotic drugs to rat and human hepatic stellate cells

et al. 1999

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The hallmark of liver fibrosis is an increased extracellular matrix deposition, caused by an activation of hepatic stellate cells (HSC). Therefore, this cell type is an important target for pharmacotherapeutic intervention. Antifibrotic drugs are not efficiently taken up by HSC or may produce unwanted side-effects outside the liver. Cell-specific delivery can provide a solution to these problems, but a specific drug carrier for HSC has not been described until now. The mannose 6-phosphate/insulin-like growth factor II (M6P/ IGF-II) receptor, which is expressed in particular upon HSC during fibrosis, may serve as a target-receptor for a potential carrier. The aim of the present study was to examine if human serum albumin (HSA) modified with mannose 6-phosphate (M6P) is taken up by HSC in fibrotic livers. A series of M6P x -modified albumins were synthetized: x ‫؍‬ 2, 4, 10, and 28. Organ distribution studies were performed to determine total liver uptake. The hepatic uptake of M6P x -HSA increased with increasing M6P density. M6P x -HSA with a low degree of sugar loading (x ‫؍‬ 2-10) remained in the plasma and accumulated for 9% ؎ 0.5% or less in fibrotic rat livers. An increase in the molar ratio of M6P: HSA to 28:1 caused an increased liver accumulation to 59% ؎ 9% of the administered dose. Furthermore, we determined quantitatively the in vivo intrahepatic distribution of M6P x -HSA using double-immunostaining techniques. An increased substitution of M6P was associated with an increased accumulation in HSC; 70% ؎ 11% of the intrahepatic staining for M6P 28

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“…[8][9][10] Lysosomal sorting via M6P/IGF2R is generally far more efficient than by MPR46, demonstrating that the former is the main lysosomal targeting receptor in mammalian cells. 11,12 However, M6P/IGF2R also binds a variety of other factors that impinge on the proliferation, migration and invasiveness of tumour cells, including insulin-like growth factor II (IGF-II), 13 transforming growth factor b, 14 urokinase-type plasminogen activator receptor 15 and plasminogen. 16 Hence, it is of high relevance that the M6P/IGF2R gene is frequently inactivated in human and animal tumours.…”

mentioning

confidence: 99%

The mannose 6‐phosphate/insulin‐like growth factor II receptor restricts the tumourigenicity and invasiveness of squamous cell carcinoma cells

Probst¹,

Puxbaum²,

Svoboda³

et al. 2009

Intl Journal of Cancer

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The mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) mediates biosynthetic sorting and endocytosis of various factors that impinge on the proliferation, migration and invasiveness of tumour cells. The gene encoding M6P/IGF2R is frequently lost or mutated in a wide range of malignant tumours including squamous cell carcinomas. We have previously shown that M6P/IGF2R-deficient SCC-VII murine squamous cell carcinoma cells secrete large amounts of pro-invasive lysosomal proteinases. Furthermore, the formation of mature lysosomes is impaired in SCC-VII cells. To assess the link between M6P/ IGF2R status and tumour invasion, we have now generated SCC-VII lines stably transfected with human M6P/IGF2R cDNA. Reconstitution of functional M6P/IGF2R expression in SCC-VII cells strongly improves the intracellular retention of lysosomal proteinases and restores the formation of mature lysosomes. In addition, the presence of heterologous M6P/IGF2R compromises the growth of SCC-VII cells both in vitro and in vivo. Remarkably, M6P/IGF2R expression also reduces the invasive capacity of SCC-VII cells in response to various chemoattractants. These results indicate that the M6P/IGF2R status influences the metastatic propensity of squamous cell carcinomas. ' 2008 Wiley-Liss, Inc.Key words: cathepsin; lysosome; proteolysis; squamous cell carcinoma; tumour invasion A key requirement for metastatic cancer cell invasion is the penetration of extracellular matrix (ECM) barriers. This process involves the degradation of different ECM proteins and proteoglycans. 1,2 Various proteinases have been implicated in ECM degradation associated with tumour invasion and metastasis, including urokinase-type plasminogen activator, matrix metalloproteinases and cathepsins. [3][4][5] The involvement of the latter enzymes in ECM proteolysis is perplexing, since cathepsins are normally localized in lysosomes. However, tumour cells often secrete significant amounts of these proteinases into the pericellular fluid, as first observed for cathepsin B. 6 As typical for lysosomal enzymes, the N-glycan moieties of cathepsins are modified during their biosynthesis with mannose 6-phosphate (M6P) residues which permit interaction with the main lysosomal sorting receptors, the 300-kDa mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) and the 46-kDa mannose 6-phosphate receptor (MPR46). 7 Evidence has been provided that excessive secretion of cathepsins by tumour cells may be due to transformation-induced changes to the M6P receptor pathway. [8][9][10] Lysosomal sorting via M6P/IGF2R is generally far more efficient than by MPR46, demonstrating that the former is the main lysosomal targeting receptor in mammalian cells. 11,12 However, M6P/IGF2R also binds a variety of other factors that impinge on the proliferation, migration and invasiveness of tumour cells, including insulin-like growth factor II (IGF-II), 13 transforming growth factor b, 14 urokinase-type plasminogen activator receptor 15 and plasminogen. 16 Hence, it is o...

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Interactions of recombinant and platelet transforming growth factor-β1 precursor with the insulin-like growth factor II/mannose 6-phosphate receptor

Cited by 128 publications

References 29 publications

Insulin-like growth factor II/mannose 6-phosphate-receptor expression in liver and serum during acute CCl4 intoxication in the rat

Insulin-like growth factor II/mannose 6-phosphate-receptor expression in liver and serum during acute CCl4 intoxication in the rat

Albumin modified with mannose 6-phosphate: A potential carrier for selective delivery of antifibrotic drugs to rat and human hepatic stellate cells

The mannose 6‐phosphate/insulin‐like growth factor II receptor restricts the tumourigenicity and invasiveness of squamous cell carcinoma cells

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