Open Access

Heparanase from triple‑negative breast cancer and platelets acts as an enhancer of metastasis

  • Authors:
    • Wen‑Jing Yang
    • Gan‑Lin Zhang
    • Ke‑Xin Cao
    • Xiao‑Ni Liu
    • Xiao‑Min Wang
    • Ming‑Wei Yu
    • Jin‑Ping Li
    • Guo‑Wang Yang
  • View Affiliations

  • Published online on: August 27, 2020     https://doi.org/10.3892/ijo.2020.5115
  • Pages: 890-904
  • Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.
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October-2020
Volume 57 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Yang WJ, Zhang GL, Cao KX, Liu XN, Wang XM, Yu MW, Li JP and Yang GW: Heparanase from triple‑negative breast cancer and platelets acts as an enhancer of metastasis. Int J Oncol 57: 890-904, 2020
APA
Yang, W., Zhang, G., Cao, K., Liu, X., Wang, X., Yu, M. ... Yang, G. (2020). Heparanase from triple‑negative breast cancer and platelets acts as an enhancer of metastasis. International Journal of Oncology, 57, 890-904. https://doi.org/10.3892/ijo.2020.5115
MLA
Yang, W., Zhang, G., Cao, K., Liu, X., Wang, X., Yu, M., Li, J., Yang, G."Heparanase from triple‑negative breast cancer and platelets acts as an enhancer of metastasis". International Journal of Oncology 57.4 (2020): 890-904.
Chicago
Yang, W., Zhang, G., Cao, K., Liu, X., Wang, X., Yu, M., Li, J., Yang, G."Heparanase from triple‑negative breast cancer and platelets acts as an enhancer of metastasis". International Journal of Oncology 57, no. 4 (2020): 890-904. https://doi.org/10.3892/ijo.2020.5115