title: Suppression of endoplasmic reticulum stress-induced invasion and migration of breast cancer cells through the downregulation of heparanase.
abstract: Tumor metastasis is the ultimate stage of cancer, and the primary cause of mortality in patients. Tumor cells breaking through the natural barrier consisting of the basement membrane (BM) and extracellular matrix (ECM) is the a crucial step in tumor invasion and metastasis. Thus, protecting this barrier is the key to reducing mortality. Heparanase is a mammalian endo-β-glucuronidase which has been found to promote the cleavage of heparan sulfate (HS), and plays a significant role in tumor cell invasion and metastasis. Although chemotherapeutic reagents have a strong antitumor activity, they may promote the invasion and migration of cancer cells, as has been observed during clinical treatment. Chemotherapeutic reagents can induce endoplasmic reticulum (ER) stress; in this study, we used adriamycin (ADM) and a classical ER stress inducer, tunicamycin (TM). We report that the activation of ER stress is involved in the enhanced invasion and migration ability of breast cancer cells and we hypothesized that this effect is associated with the activation of heparanase. In support of this, we used the heparanase inhibitor, OGT2115, and low molecular weight heparin (LMWH) to inhibit the expression and activity of heparanase, and we found that the invasion and migration ability of the cells was suppressed. Our findings demonstrate that heparanase inhibitors suppress breast cancer cell invasion and migration induced by ER stress, and provide a strong rationale for the development of heparanase-based therapeutics for the prevention of metastasis induced by chemotherapeutic reagents.
authors: Faculty of Pharmacy, Bengbu Medical College, Bengbu, Anhui 233000, P.R. China.
authors: Yang
authors: Y
authors: Li
authors: Hao
authors: H
authors: Liu
authors: Ying Ying
authors: YY
authors: Huang
authors: Long Jian
authors: LJ
authors: Pu
authors: Xu Dong
authors: XD
authors: Zhang
authors: Chen Chen
authors: CC
authors: Jiang
authors: Zhi Wen
authors: ZW
authors: Jiang
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005966:Glucuronidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology; D006801:Humans; D009361:Neoplasm Invasiveness; D014415:Tunicamycin / Q000494:pharmacology; D000099175:Heparanase
chemical_list: D004317:Doxorubicin; D005966:Glucuronidase; D006495:Heparin, Low-Molecular-Weight; D014415:Tunicamycin; D000099175:Heparanase