Heparanase enhances tumor growth and chemoresistance by promoting autophagy

Anna Shteingauz1, Ilanit Boyango1, Inna Naroditsky2, Edward Hammond3, Maayan Gruber4, Ilana Doweck4, Neta Ilan1, and Israel Vlodavsky1

Cancer Res. 2015 Sep 15;75(18):3946-57.

Speaker: Chun-I Li (李俊毅)                                    Time: 14:00~15:00, Nov, 25, 2015

Commentator: Dr. Chih-Peng Chang (張志鵬 教授)  Place: Room 601

Abstract：

    Heparanase, an endo-b-glucuronidase, has ability to cleave heparin sulfate and leads to disassembly of the extracellular matrix . It also results in fundamental biologic phenomena associated with inflammation, angiogenesis, tissue remodeling, cell invasion, and metastasis (1). However, little is known about role of haparanase under normal conditions. Heparanase primarily resides within endocytic vesicles, which showed a polar, perinuclear localization and colocalization with lysosome (2). Heparanase also enhances exosome secretion that contribute to tumor growth (3). Autophagy is an intracellular degradation and energy ecycling mechanism through which cytoplasmic components are sequestered into the double- membrane vesicles called autophagosomes. In this study, the authors reported that heparanase resides within autophagosomes and colocalizes with lysosome. Transgenic mice or mice with heparanase-deficient established the contributions of heparanase to autophagy. The authors revealed that heparanase not only resides in autophagosomes but also regulates autophagy. In conclusion, the authors provide evidence that heparanase plays a promoting role in tumorigenesis and chemoresistance by induction of autophagy.

References：

1.     Ilan N, Elkin M, Vlodavsky I. (2006) Regulation, function and clinical significance of heparanase in cancer metastasis and angiogenesis. Intl J Biochem Cell

Biol. 38, 2018–2039.

2.     Gingis-Velitski S, Zetser A, Kaplan V, Ben-Zaken O, Cohen E, Levy-Adam F, Bashenko Y, Flugelman MY, Vlodavsky I, Ilan N (2004) Heparanase uptake is mediated by cell membrane heparan sulfate proteoglycans. J Biol Chem. 279, 44084–44092.

3.     Thompson CA, Purushothaman A, Ramani VC, Vlodavsky I, Sanderson RD. (2013) Heparanase regulates secretion, composition, and function of tumor cell-derived exosomes. J Biol Chem. 288, 10093–10099.