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- Zhao, YufangHarbin Inst Technol, Sch Life Sci & Technol, Harbin 150080, Heilongjiang, Peoples R China.;Harbin Inst Technol, Res Ctr Basic Space Sci, Space Environm Stimulat & Res Interface, Harbin 150080, Heilongjiang, Peoples R China. (author)
Bioengineered tumor microenvironments with naked mole rats high-molecular-weight hyaluronan induces apoptosis in breast cancer cells
- Article/chapterEnglish2019
Publisher, publication year, extent ...
- 2019-01-30
- NATURE PUBLISHING GROUP,2019
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- LIBRIS-ID:oai:DiVA.org:kth-270657
- https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-270657URI
- https://doi.org/10.1038/s41388-019-0719-4DOI
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- Language:English
- Summary in:English
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- QC 20200327
- The naked mole rat (nmr) is cancer resistant due to the abundant production of extremely high-molecular-weight hyaluronan (EHMW-HA). However, whether EHMW-HA has similar anti-cancer effects in mice and humans remains to be determined. The present study used breast cancer cells to clarify the effect of EHMW-HA on breast cancer. First, the overexpression of nmrHas2 in 4T1 and BT549 cell lines in both two-dimensional (2D) and three-dimensional (3D) models to mimic tumor microenvironment was established. The 4T1/BT549-nmrHas2 cells could secrete EHMW-HA (with a molecular weight of up to 6 MDa), which was similar to that found in the naked mole rat. Second, EHMW-HA altering tumor microenvironment in both 2D monolayers and 3D spheroids significantly enhanced apoptosis, inhibiting the proliferation of 4T1 and BT549 cells. The prominent anticancer effects of EHMW-HA on the cancer-cell apoptosis phenotype were further confirmed by inhibiting tumor formation in nude mice. Finally, EHMW-HA significantly induced higher p53 protein expression, which enhanced pro-apoptotic proteins p21 and Bax in breast cancer cells; this is in contrast with the triggering of hypersensitivity of the naked mole rat cells to early contact inhibition (ECI). These results have important implications for the design of therapeutic approaches based on the application of EHMW-HA.
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- Qiao, ShupeiHarbin Inst Technol, Sch Life Sci & Technol, Harbin 150080, Heilongjiang, Peoples R China. (author)
- Hou, XiaoluHarbin Inst Technol, Sch Life Sci & Technol, Harbin 150080, Heilongjiang, Peoples R China. (author)
- Tian, HuiHarbin Inst Technol, Sch Life Sci & Technol, Harbin 150080, Heilongjiang, Peoples R China. (author)
- Deng, ShuaiHarbin Inst Technol, Sch Life Sci & Technol, Harbin 150080, Heilongjiang, Peoples R China. (author)
- Ye, KangruoHarbin Inst Technol, Sch Life Sci & Technol, Harbin 150080, Heilongjiang, Peoples R China. (author)
- Nie, YongzhanFourth Mil Med Univ, State Key Lab Canc Biol, Harbin 150080, Heilongjiang, Peoples R China.;Fourth Mil Med Univ, Xijing Hosp Digest Dis, Harbin 150080, Heilongjiang, Peoples R China. (author)
- Chen, XiongbiaoUniv Saskatchewan, Dept Mech Engn, Saskatoon, SK S7N 5A2, Canada. (author)
- Yan, HongjiKTH,Glykovetenskap(Swepub:kth)u1qjm063 (author)
- Tian, WeimingHarbin Inst Technol, Sch Life Sci & Technol, Harbin 150080, Heilongjiang, Peoples R China. (author)
- Harbin Inst Technol, Sch Life Sci & Technol, Harbin 150080, Heilongjiang, Peoples R China.;Harbin Inst Technol, Res Ctr Basic Space Sci, Space Environm Stimulat & Res Interface, Harbin 150080, Heilongjiang, Peoples R China.Harbin Inst Technol, Sch Life Sci & Technol, Harbin 150080, Heilongjiang, Peoples R China. (creator_code:org_t)
Related titles
- In:Oncogene: NATURE PUBLISHING GROUP38:22, s. 4297-43090950-92321476-5594
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