Heparanase

Proteases and their involvement in cancer progression have been well addressed and documented; however, the emerging premise presented within this book is that Heparanase is a master regulator of aggressive cancer phenotypes and crosstalk with the tumor microenvironment. This endoglycosidase contributes to tumor-mediated remodeling of the extracellular matrix and cell surfaces, augmenting the bioavailability of pro-tumorigenic and pro-inflammatory growth factors and cytokines that are bound to Heparan sulfate. Compelling evidence ties Heparanase with all steps of tumor progression including tumor initiation, growth, angiogenesis, metastasis, and chemoresistance, supporting the notion that Heparanase is an important contributor to the poor outcome of cancer patients and a validated target for therapy. Unlike Heparanase, heparanase-2, a close homolog of Heparanase, lacks enzymatic activity, inhibits Heparanase, and regulates selected genes that promote normal differentiation and tumor suppression. Written by internationally recognized leaders in Heparanase biology, this volume presents a comprehensive understanding of Heparanase's multifaceted activities in cancer, inflammation, diabetes and other diseases, as well as its related clinical applications to scientists, clinicians and advanced students in cell biology, tumor biology and oncology.

Auteur
Israel Vlodavsky is a Professor of Cancer and Vascular Biology at Technion- Israel Institute of Technology's Rappaport Faculty of Medicine and Technion Integrated Cancer Center (TICC). Vlodavsky's discovery of the extracellular matrix as a reservoir for bioactive molecules provided the basis for the current appreciation of the tumor microenvironment and its significance in cancer progression and treatment. A pioneering achievement of Vlodavsky is the cloning and characterization of heparanase, the predominant enzyme that degrades heparan sulfate and fulfills important roles in tissue remodeling, cancer metastasis, angiogenesis, inflammation, diabetes, and kidney dysfunction. Through the combination of basic and translational research, Vlodavsky is the leading scientist in this area of research, offering basic insights and new treatment strategies for various cancers and other diseases. He earned his bachelor's and Master's degrees from The Hebrew University of Jerusalem, and Ph.D. from the Weizmann Institute, Rehovot, Israel. Ralph Sanderson is the UAB Endowed Professor of Cancer Pathobiology and Director, Division of Molecular and Cellular Pathology, Department of Pathology, UAB O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham. Sanderson earned a B.S. from the University of Alabama, and a Ph.D. at the University of Alabama at Birmingham. His research focuses on determining how tumor-host cell interactions mediated by heparan sulfate and the enzyme heparanase regulate the tumor microenvironment and promote tumor progression, and to use that knowledge to design new cancer therapies.
Neta Ilan is a Senior Researcher at the Rappaport Faculty of Medicine and the Technion Integrated Cancer Center (TICC), Haifa, Israel. Neta earned a bachelor's degree in Agricultural Sciences and a Master's degree in Biotechnology from the Hebrew University of Jerusalem. Neta completed his education at the Hebrew University, with a doctorate in Animal Sciences, working on manipulation of the mammary gland of transgenic animals. He did his postdoctoral training at Yale University, focusing on tumor angiogenesis. His current research focuses on the mode of action and role of heparanase in cancer initiation, growth, and metastasis in order to address problems in the prevention, management, and treatment of cancer.

Résumé

Written by internationally recognized leaders in Heparanase biology, the book's eight chapters offer an opportunity for scientists, clinicians and advanced students in cell biology, tumor biology and oncology to obtain a comprehensive understanding of Heparanase's multifaceted activities in cancer, inflammation, diabetes and other diseases, as well as its related clinical applications.

Proteases and their involvement in cancer progression have been well addressed and documented; however, the emerging premise presented within this book is that Heparanase is a master regulator of aggressive cancer phenotypes and crosstalk with the tumor microenvironment. This endoglycosidase contributes to tumor-mediated remodeling of the extracellular matrix and cell surfaces, augmenting the bioavailability of pro-tumorigenic and pro-inflammatory growth factors and cytokines that are bound to Heparan sulfate. Compelling evidence ties Heparanase with all steps of tumor progression including tumor initiation, growth, angiogenesis, metastasis, and chemoresistance, supporting the notion that Heparanase is an important contributor to the poor outcome of cancer patients and a validated target for therapy. Unlike Heparanase, heparanase-2, a close homolog of Heparanase, lacks enzymatic activity, inhibits Heparanase, and regulates selected genes that promote normal differentiation and tumor suppression. Written by internationally recognized leaders in Heparanase biology, this volume presents a comprehensive understanding of Heparanase's multifaceted activities in cancer, inflammation, diabetes and other diseases, as well as its related clinical applications to scientists, clinicians and advanced students in cell biology, tumor biology and oncology.

Contenu

Historical background

1. Mast cell/platelet heparanase/Heparan sulfate biosynthesis and turnover

2. Gene cloning/overview

3. Gene cloning/melanoma metastasis

4. Gene cloning/cancer/immune system

5. Heparin/HS modifying enzymes

Crystal structure/substrate specificity/gene regulation

6. Crystal structure

7. Molecular dynamics, KKDC peptide

8. Biochemistry/active site

9. Substrate specificity

10.Gene regulation, promoter/Egr1/methylation

11. SNPs - polymorphism

12. Splice variants

Cell & tumor biology (general functions & mode of action)

13 Exosomes/heparan sulfate/heparanase

14. Exosomes/drug resistance

15. Nuclear heparanase/transcriptional activity

16. Non-enzymatic functions/signal transduction/cellular trafficking/autophagy

17. Heparan sulfate/stem cells/inflammation

18. Danger signals/HS/platelet heparanase

19. Heparanase/integrins/melanoma

Immune cells/immuno-modulation

20. Heparin, heparanase & selectins in cancer metastasis and inflammation

21Trans-endithelial migration, lymphocytes/neutrophils/t-cells

22 Macrophages/ dendritic cells/autoimmunity

23. Macrophages, Heparanase and the tumor microenvironment, neutralizing antibodies

24. NK cells

Cancer (heparanase in specic types of cancer)

25. Myeloma/inhibition/drug resistance

26. Breast cancer/pancreatic cancer/Cancer & Inflammation

27 Brain metastasis/mir-1258

28. Gastric cancer/immunization

29. Head & Neck

30. Glioma 31.Sarcoma

Inhibitors/clinical trials/cancer

32. Chemistry/synthesis of heparanase inhibitors PI-88, PG

33. PG series; biology. Tumor models & clinical trial

34 Chemically modified heparins/ Heparin mimetics

35. Roneparstat/small molecules/clinical trials

Other indications/diseases

36.IBD/inflammation & cancer/diabetes/obesity

37 immune diabetes

38. Inflammation, Sepsis/Amyloidosis

39. Kidney dysfunction

40. Fibrosis

41. Viral infection

42. Cariomyocytes/ Endothelial cell-cardiomyocyte crosstalk in diabetic cardiomyopathy

43. Eye research

44. Atherosclerosis, nuclear localization

45. Coagulation/tissue factor

Heparanase-2 (Hpa2)

46. Hpa2 gene cloning

47. UFS - urofacial syndrome; peripheral neuropathy

48. Hpa2: t…