TY - JOUR AB - Triple‑negative breast cancer (TNBC), which is characterized by inherently aggressive behavior and lack of recognized molecular targets for therapy, poses a serious threat to women's health worldwide. However, targeted treatments have yet to be made available. A crosstalk between tumor cells and platelets (PLT) contributing to growth, angiogenesis and metastasis has been reported in numerous cancers. Heparanase (Hpa), the only mammalian endoglycosidase that cleaves heparan sulfate, has been demonstrated to contribute to the growth, angiogenesis and metastasis of numerous cancers. Hypoxia affects the growth, angiogenesis and metastasis of nearly all solid tumors, and the ability of Hpa to promote invasion is enhanced in hypoxia. However, whether Hpa can strengthen the crosstalk between tumor cells and PLT, and whether enhancing the biological function of Hpa in TNBC promotes malignant progression, have yet to be fully elucidated. The present study, based on bioinformatics analysis and experimental studies in vivo and in vitro, demonstrated that Hpa enhanced the crosstalk between TNBC cells and PLT to increase the supply of oxygen and nutrients, while also conferring tolerance of TNBC cells to oxygen and nutrient shortage, both of which are important for overcoming the stress of hypoxia and nutritional deprivation in the tumor microenvironment, thereby promoting malignant progression, including growth, angiogenesis and metastasis in TNBC. In addition, the hypoxia‑inducible factor‑1a (HIF-1a)/vascular endothelial growth factor‑a (VEGF- a)/phosphorylated protein kinase B (p-)Akt axis may be the key pathway involved in the effects of Hpa on the biological processes mentioned above. Therefore, improving local hypoxia, anti‑Hpa treatment and inhibiting PLT activation may improve the prognosis of TNBC. AD - Department of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, P.R. China Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing 100069, P.R. China Biomedical Center, Uppsala University, Uppsala 75123, Sweden AU - Yang,Wen‑Jing AU - Zhang,Gan‑Lin AU - Cao,Ke‑Xin AU - Liu,Xiao‑Ni AU - Wang,Xiao‑Min AU - Yu,Ming‑Wei AU - Li,Jin‑Ping AU - Yang,Guo‑Wang DA - 2020/10/01 DO - 10.3892/ijo.2020.5115 EP - 904 IS - 4 JO - Int J Oncol KW - triple‑negative breast cancer platelets heparanase hypoxia metastasis PY - 2020 SN - 1019-6439 1791-2423 SP - 890 ST - Heparanase from triple‑negative breast cancer and platelets acts as an enhancer of metastasis T2 - International Journal of Oncology TI - Heparanase from triple‑negative breast cancer and platelets acts as an enhancer of metastasis UR - https://doi.org/10.3892/ijo.2020.5115 VL - 57 ER -