Open AccessTranslocation of heparanase into nucleus results in cell differentiation
Author(s) -
Nobuhisa Tetsuji,
Naomoto Yoshio,
Okawa Takaomi,
Takaoka Munenori,
Gunduz Mehmet,
Motoki Takayuki,
Nagatsuka Hitoshi,
Tsujigiwa Hidetsugu,
Shirakawa Yasuhiro,
Yamatsuji Tomoki,
Haisa Minoru,
Matsuoka Junji,
Kurebayashi Junichi,
Nakajima Motowo,
Taniguchi Shun’ichiro,
Sagara Junji,
Dong Jian,
Tanaka Noriaki
Publication year - 2007
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2007.00420.x
Subject(s) - heparanase , chromosomal translocation , microbiology and biotechnology , cytoplasm , extracellular matrix , cancer cell , cell , biology , cancer , chemistry , cancer research , heparan sulfate , biochemistry , genetics , gene
We recently reported that heparanase, one of the extracellular matrix‐degrading enzymes, which plays a critical role in cancer progression, is located not only in the cytoplasm but also in the nucleus. Here we identified nuclear translocation of heparanase as a key step in cell differentiation. We applied an in vitro differentiation model of HL‐60 cells with 12–0‐tetradecanoylphorbol‐13‐acetate (TPA), in which nuclear translocation of heparanase was observed using immunohistochemical analysis. In this system, nuclear translocation of heparanase was abolished by inhibitors of heat shock protein 90 (HSP90), suggesting the involvement of HSP90 in translocation of heparanase. We further confirmed that overexpression of active form of heparanase induced differentiation of HL‐60 cells, although the catalytic negative form of heparanase did not. Therefore we speculate that nuclear translocation of enzymatically active heparanase may be involved in cellular differentiation. Our results suggest that a novel function of heparanase upon cell differentiation would raise a potential new strategy for cancer therapy of promyeloid leukemia and other types of cancer. ( Cancer Sci 2007; 98: 535–540)