Human Heparanase-1 Gene Expression in Pancreatic Adenocarcinoma

Kim, Anthony W.; Xu, Xiulong; Hollinger, Edward F.; Gattuso, Paolo; Godellas, Constantine V.; Prinz, Richard A.

doi:10.1016/s1091-255x(01)00087-7

Cited by 58 publications

(36 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HB-EGF is able to bind to EGF receptors, the main target of the tyrosine kinase inhibitors (11), with a higher affinity than EGF itself and has recently been discussed as a potential molecular target (12,13). Heparanase (HPSE) functions as an endoglycosidase that cleaves heparan sulfate chains of proteoglycans (14,15). Enclosed in the heparan sulfate glycosaminoglycans are growth factors and angiogenic factors, like basic fibroblast growth factor (bFGF) and HB-EGF that are released upon degradation with HPSE (16).…”

mentioning

confidence: 99%

A Three-Gene Signature for Outcome in Soft Tissue Sarcoma

Hoffmann

Danenberg

Täubert

et al. 2009

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Finding markers or gene sets that would further classify patients into different risk categories and thus allow more individually adapted multimodality treatment regimens in soft tissue sarcomas is necessary. In this study, we investigated the prognostic values of hypoxia-inducible factor 1a (HIF1a), heparin-binding epidermal growth factor–like growth factor (HB-EGF), vascular endothelial growth factor (VEGF), and other angiogenesis-related gene expressions, as well as their interrelationships. Experimental Design: Formalin-fixed paraffin-embedded tissue samples were obtained from 45 patients with soft tissue sarcoma (median age 57 years, range 16–85 years). After laser capture microdissection direct quantitative real-time reverse transcription-PCR (TaqMan) assays were done in triplicates to determine HIF1a, HB-EGF, VEGF, and other gene expression levels. Results: Multivariate Cox regression analysis revealed significant independent associations of HB-EGF, HIF1a, and VEGF-C gene expression to the overall survival (P < 0.0001). A combined factor of these three genes showed a relative risk for shorter survival of 5.5, more than twice higher as in an increasing International Union against Cancer Stage. Receiver operating characteristic curve analysis showed a significant sensitivity of 73% and specificity of 82% of this factor for the diagnosis of short (<3 years) versus long (3-9 years) survival (P = 0.0002). VEGF-A showed significant gender differences in the association to survival. Conclusions: Measuring HIF1a, HB-EGF, and VEGF-C expression may contribute to a better understanding of the prognosis of patients with soft tissue sarcoma and may even play a crucial role for the distribution of patients to multimodal therapeutic regimens. Prospective studies investigating the response to different adjuvant or palliative therapies seem to be warranted. (Clin Cancer Res 2009;15(16):5191–8)

show abstract

mentioning

confidence: 99%

A Three-Gene Signature for Outcome in Soft Tissue Sarcoma

Hoffmann

Danenberg

Täubert

et al. 2009

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…Heparanase up regulation documented in an increasing number of human malignancies [14][15][16][17][18][19][20][21], as well as in several other pathologies [22][23][24], and the cloning of the same human heparanase cDNA sequence by various laboratories [42][43][44][45] suggest that a single prominent HS-degrading endoglycosidase is expressed by mammalian cells, positioning heparanase as a potentially new and promising drug target. Several assays have been developed for quantifying heparanase enzymatic activity, detecting the degradation of fluorescent or radiolabeled HS chains [26,29,31,46], or the degradation of intact, metabolically sulfate labeled ECM deposited by cultured cells [27].…”

Section: Discussionmentioning

confidence: 99%

“…Fractions (0.2 ml) were eluted with PBS and their radioactivity counted in a β-scintillation counter. Degradation fragments of HS side chains are eluted at 0.5< K av <0.8 (peak II, fractions [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] and represent heparanase generated degradation products [33,37].…”

Section: Methodsmentioning

confidence: 99%

“…Traditionally correlated with the metastatic potential of cancer cells, heparanase up regulation has been demonstrated in an increasing number of primary human tumors, correlating with reduced post operative survival rates [14][15][16][17][18][19][20][21]. Heparanase is also up regulated in diabetic nephropathy [22,23].…”

Section: Heparanase Elisa As a Diagnostic Toolmentioning

confidence: 99%

“…This notion recently gained further support by employing siRNA and ribozyme technologies, clearly depicting heparanase-mediated HS cleavage and ECM remodeling as critical requisites for metastatic spread [13]. Since the cloning of the heparanase gene and the availability of specific molecular probes, heparanase upregulation was documented in an increasing number of primary human tumors, correlating with reduced postoperative survival, enhanced local and distant metastasis and increased microvessel density [14][15][16][17][18][19][20][21]. The enzyme has also been implicated in diabetic nephropathy [22,23] and immune responses [2,11,12,24].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

An ELISA method for the detection and quantification of human heparanase

Shafat¹,

Zcharia

Nisman

et al. 2006

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

Heparanase is a mammalian endo-β-D-glucuronidase that cleaves heparan sulfate (HS) side chains at a limited number of sites. Heparanase enzymatic activity is thought to participate in degradation and remodeling of the extracellular matrix (ECM) and to facilitate cell invasion associated with tumor metastasis, angiogenesis and inflammation. Traditionally, heparanase activity was well correlated with the metastatic potential of a large number of tumor-derived cell types. More recently, heparanase up regulation was detected in an increasing number of primary human tumors, correlating, in some cases, with poor postoperative survival and increased tumor vascularity. The present study was undertaken to develop a highly sensitive ELISA assay suitable for the determination and quantification of human heparanase in tissue extracts and body fluids. The assay preferentially detects the 8+50 kDa active heparanase heterodimer vs. the latent 65 kDa pro-enzyme and correlates with immunoblot analysis of heparanase containing samples. It detects heparanase at concentrations as low as 200 pg/ml, and is suitable for quantification of heparanase in tissue extracts and urine.

show abstract

Elevated serum heparanase‐1 levels in patients with pancreatic carcinoma are associated with poor survival

Quiros

Rao

Plate

et al. 2005

Cancer

View full text Add to dashboard Cite

BACKGROUND It has previously been shown that heparanase‐1 (HPR1), an endoglycosidase, is up‐regulated in pancreatic carcinoma. The purpose of this study was to test whether serum HPR1 levels in pancreatic carcinoma patients are elevated, and whether higher serum HPR1 levels are associated with a shortened survival. METHODS Serum HPR1 levels in 40 healthy donors, 31 pancreatic carcinoma patients, and 11 patients treated with gemcitabine were measured by a novel enzyme‐linked immunoadsorbent assay. HPR1 expression in tumors was analyzed by immunohistochemical staining. Patient overall survival time was determined according to the Kaplan–Meier method, and their difference was evaluated by the log‐rank test. A P value < 0.05 was considered statistically significant. RESULTS The mean serum HPR1 activity in pancreatic carcinoma patients was 439 ± 14 units/mL, compared with 190 ± 4 units/mL in the control serum samples from healthy donors. Serum HPR1 levels were significantly higher in patients with HPR1‐positive tumors (660 ± 62 units/mL) compared with those with HPR1‐negative tumors (241 ± 14 units/mL). The mean survival of 19 pancreatic carcinoma patients with serum HPR1 activity > 300 units/mL was 7.9 ± 0.2 months, whereas the mean survival of 12 patients with serum HPR1 activity < 300 units/mL was 13.3 ± 0.6 months. A Kaplan–Meier plot of the patient survival curve followed by log‐rank test revealed that patients in the high serum HPR1 group had a significantly shorter survival compared with those in the low serum HPR1 group. Mean serum HPR1 activity decreased by 64% in 11 pancreatic carcinoma patients after 2 weeks of treatment with gemcitabine. CONCLUSIONS Serum HPR1 activity in pancreatic carcinoma patients was found to be significantly elevated, in particular in those with HPR1‐positive tumors. Increased serum HPR1 activity was associated with a shorter survival in patients with pancreatic carcinoma patients. Cancer 2006. © 2005 American Cancer Society.

show abstract

Human Heparanase-1 Gene Expression in Pancreatic Adenocarcinoma

Cited by 58 publications

References 19 publications

A Three-Gene Signature for Outcome in Soft Tissue Sarcoma

A Three-Gene Signature for Outcome in Soft Tissue Sarcoma

An ELISA method for the detection and quantification of human heparanase

Elevated serum heparanase‐1 levels in patients with pancreatic carcinoma are associated with poor survival

Contact Info

Product

Resources

About