Degradation of Basement Membrane by Prostate Tumor Heparanase

Kosir, Mary A.; Wang, Wenlian; Zukowski, Kim; Tromp, Gerard; Barber, Joseph

doi:10.1006/jsre.1998.5519

Cited by 31 publications

(23 citation statements)

References 19 publications

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“…Hpa expression was recently suggested to be associated with the metastatic potential of human tumors, such as pancreatic adenocarcinoma (30,31), breast cancer (12), and others (32,33). 4 C. Choi, P. Beckhove, and V. Schirrmacher, unpublished observation.…”

Section: Discussionmentioning

confidence: 99%

Heparanase: A New Metastasis-Associated Antigen Recognized in Breast Cancer Patients by Spontaneously Induced Memory T Lymphocytes

Sommerfeldt

Beckhove

et al. 2006

Cancer Research

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Increased expression and secretion of heparanase (Hpa) by tumor cells promotes tumor invasion through extracellular matrices, tissue destruction, angiogenesis, and metastasis. Here, we show the existence in breast cancer patients of Hpaspecific T lymphocytes by fluorescence-activated cell sorting flow cytometry using Hpa peptide-MHC class I tetramers. We furthermore show memory T-cell responses in a high proportion of breast cancer patients to Hpa-derived HLA-A2-restricted peptides, leading to production of IFN-; and to generation of antitumor CTLs lysing breast cancer cells. Such CTLs recognized endogenously processed respective Hpa peptides on Hpa-transfected and Hpa-expressing untransfected breast carcinoma cells. According to these results and to the fact that such cells were not found in healthy people, Hpa seems to be an attractive new tumor-associated antigen and its HLA-A2-restricted peptides ought to be good candidates for peptide vaccination to reactivate memory immune responses to invasive and metastatic cancer cells. (Cancer Res 2006; 66(15): 7716-23)

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Section: Discussionmentioning

confidence: 99%

Heparanase: A New Metastasis-Associated Antigen Recognized in Breast Cancer Patients by Spontaneously Induced Memory T Lymphocytes

Sommerfeldt

Beckhove

et al. 2006

Cancer Research

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“…HPA expression correlates with the metastatic potential of breast cancers [17] , and antisensemediated suppression of human heparanase gene expression may inhibit pleural dissemination of human cancer cells [18] . It has been found that high levels of HPA can be detected in a variety of malignant tissues or cells with high malignance or powerfully metastatic potential, among which are lymphoma, fibrosarcoma [9,19] ,oral cancer cell lines and oral cancer [20] , esophageal carcinomas [21] , lung cancer [18,22] ,malignant melanoma [19,23,24] ,breast cancer [9,25] ,gastric carcinoma and carcinoma of colon [26,27] , pancreatic carcinoma [28,29] , prostate cancer [30] ,bladder carcinoma [31] , pheochromocytoma and ovarian cancer, and that no or only very weak HPA could be observed in some tumor cells with low or no metastatic potential. We detected the HPA mRNA expression of cancerous tissues in 33 HCC patients, and found that it was positive in 16 HCC samples (48.5%, 16/33).…”

Section: Discussionmentioning

confidence: 99%

Heparanase mRNA expression and point mutation in hepatocellular carcinoma

Chen

Liu²,

Rui³

et al. 2004

WJG

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AIM:To explore the expression of heparanase mRNA and point mutation in hepatocellular carcinoma (HCC). METHODS:Reverse transcription polymerase chain reaction was used to measure the expression of heparanase mRNA in the primary tumor tissues and surrounding liver tissues of 33 HCC patients. T-A cloning and sequencing were used to detect whether there was any mutation in the amplified PCR products. RESULTS:The expression of heparanase mRNA was positive in 16 primary tumor tissues of HCC, and the positive rate was 48.5%, which was significantly higher than that in the surrounding liver parenchyma (P<0.01). The positive rate for heparanase gene in high-tendency to metastatic recurrence group (71.4%, 10/14) was obviously higher than that in low-tendency to metastatic recurrence group (31.6%, 6/19) (P = 0.023). The positive rate for heparanase gene in patients with metastatic recurrence during postoperative follow-up (78.6%, 11/14) was also significantly higher than that in those without metastatic recurrence (21.4%, 3/14) (P = 0.003). Sequence analysis of the HPA PCR products was made in 7 patients, and 2-point mutations were found in 4 patients, one of which was sense mutation, neither base insertion nor deletion was detected. The mutation rate was 57.1% (4/7). CONCLUSION:The expression rate of heparanase mRNA increases in HCC, and HPA mRNA may be one of the reliable markers for the metastatic activity gained by the liver tumor cells and could be used clinically in predicting metastatic recurrence of HCC. Point mutation may be one of the causes for enhanced heparanase mRNA expression.

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“…Heparanase cleavage of HS in the ECM, particularly in epithelial and subendothelial basement membranes, is, therefore, a critical determinant in cancer development and progression (Hulett et al, 1999;Kussie et al, 1999;Toyoshima & Nakajima, 1999;Friedmann et al, 2000;El-Assal et al, 2001;Gohji et al, 2001;Koliopanos et al, 2001;Rohloff et al, 2002). Heparanase is preferentially expressed in human tumors (Kosir et al, 1999;Vlodavsky et al, 1999;Zcharia et al, 2001) in correlation with metastatic potential, tumor vascularity and reduced postoperative survival of cancer patients (Kosir et al, 1999;Friedmann et al, 2000;El-Assal et al, 2001;Gohji et al, 2001;Koliopanos et al, 2001;Zcharia et al, 2001;Rohloff et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Tumor suppressor p53 regulates heparanase gene expression

Haupt²,

et al. 2006

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Mammalian heparanase degrades heparan sulfate, the most prominent polysaccharide of the extracellular matrix. Causal involvement of heparanase in tumor progression is well documented. Little is known, however, about mechanisms that regulate heparanase gene expression. Mutational inactivation of tumor suppressor p53 is the most frequent genetic alteration in human tumors. p53 is a transcription factor that regulates a wide variety of cellular promoters. In this study, we demonstrate that wild-type (wt) p53 binds to heparanase promoter and inhibits its activity, whereas mutant p53 variants failed to exert an inhibitory effect. Moreover, p53-H175R mutant even activated heparanase promoter activity. Elimination or inhibition of p53 in several cell types resulted in a significant increase in heparanase gene expression and enzymatic activity. Trichostatin A abolished the inhibitory effect of wt p53, suggesting the involvement of histone deacetylation in negative regulation of the heparanase promoter. Altogether, our results indicate that the heparanase gene is regulated by p53 under normal conditions, while mutational inactivation of p53 during cancer development leads to induction of heparanase expression, providing a possible explanation for the frequent increase of heparanase levels observed in the course of tumorigenesis.

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Degradation of Basement Membrane by Prostate Tumor Heparanase

Cited by 31 publications

References 19 publications

Heparanase: A New Metastasis-Associated Antigen Recognized in Breast Cancer Patients by Spontaneously Induced Memory T Lymphocytes

Heparanase: A New Metastasis-Associated Antigen Recognized in Breast Cancer Patients by Spontaneously Induced Memory T Lymphocytes

Heparanase mRNA expression and point mutation in hepatocellular carcinoma

Tumor suppressor p53 regulates heparanase gene expression

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