TY - JOUR
T1 - Localization of heparanase in esophageal cancer cells
T2 - Respective roles in prognosis and differentiation
AU - Ohkawa, Takaomi
AU - Naomoto, Yoshio
AU - Takaoka, Munenori
AU - Nobuhisa, Tetsuji
AU - Noma, Kazuhiro
AU - Motoki, Takayuki
AU - Murata, Toshihiro
AU - Uetsuka, Hirokazu
AU - Kobayashi, Masahiko
AU - Shirakawa, Yasuhiro
AU - Yamatsuji, Tomoki
AU - Matsubara, Nagahide
AU - Matsuoka, Junji
AU - Haisa, Minoru
AU - Gunduz, Mehmet
AU - Tsujigiwa, Hidetsugu
AU - Nagatsuka, Hitoshi
AU - Hosokawa, Masao
AU - Nakajima, Motowo
AU - Tanaka, Noriaki
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2004/10
Y1 - 2004/10
N2 - In this study, we examined the distribution of heparanase protein in 75 esophageal squamous cell carcinomas by immunohistochemistry and analyzed the relationship between heparanase expression and clinicopathological characteristics. In situ hybridization showed that the mRNA expression pattern of heparanase was similar to that of the protein, suggesting that increased expression of the heparanase protein at the invasive front was caused by an increase of heparanase mRNA in tumor cells. Heparanase expression correlated significantly with depth of tumor invasion, lymph node metastasis, tumor node metastasis (TNM) stage and lymphatic invasion. Overexpression of heparanase in esophageal cancers was also associated with poor survival. In addition to its localization in the cytoplasm and cell membrane, heparanase was also identified in the nuclei of normal epithelial and tumor cells by immunohistochemistry. Furthermore, nuclear heparanase was detected in nuclear extract of cancer cell lines by Western blot and immunohistochemistry. Examination of the role of nuclear heparanase in cell proliferation and differentiation by double immunostaining for proliferating cell nuclear antigen (PCNA) and cytokeratin 10 (CK10) showed significant relationship between nuclear heparanase expression and differentiation (heparanase vs CK10), but not for proliferative state of esophageal cancer cells (heparanase vs PCNA). Our results suggest that cytoplasmic heparanase appears to be a useful prognostic marker in patients with esophageal cancer and that nuclear heparanase protein may play a role in differentiation. Inhibition of heparanase activity may be effective in the control of esophageal tumor invasion and metastasis.
AB - In this study, we examined the distribution of heparanase protein in 75 esophageal squamous cell carcinomas by immunohistochemistry and analyzed the relationship between heparanase expression and clinicopathological characteristics. In situ hybridization showed that the mRNA expression pattern of heparanase was similar to that of the protein, suggesting that increased expression of the heparanase protein at the invasive front was caused by an increase of heparanase mRNA in tumor cells. Heparanase expression correlated significantly with depth of tumor invasion, lymph node metastasis, tumor node metastasis (TNM) stage and lymphatic invasion. Overexpression of heparanase in esophageal cancers was also associated with poor survival. In addition to its localization in the cytoplasm and cell membrane, heparanase was also identified in the nuclei of normal epithelial and tumor cells by immunohistochemistry. Furthermore, nuclear heparanase was detected in nuclear extract of cancer cell lines by Western blot and immunohistochemistry. Examination of the role of nuclear heparanase in cell proliferation and differentiation by double immunostaining for proliferating cell nuclear antigen (PCNA) and cytokeratin 10 (CK10) showed significant relationship between nuclear heparanase expression and differentiation (heparanase vs CK10), but not for proliferative state of esophageal cancer cells (heparanase vs PCNA). Our results suggest that cytoplasmic heparanase appears to be a useful prognostic marker in patients with esophageal cancer and that nuclear heparanase protein may play a role in differentiation. Inhibition of heparanase activity may be effective in the control of esophageal tumor invasion and metastasis.
KW - Differentiation
KW - Esophageal cancer
KW - Heparanase
KW - Metastasis
KW - Nuclear localization
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U2 - 10.1038/labinvest.3700159
DO - 10.1038/labinvest.3700159
M3 - Article
C2 - 15286661
AN - SCOPUS:4944263842
VL - 84
SP - 1289
EP - 1304
JO - Laboratory Investigation
JF - Laboratory Investigation
SN - 0023-6837
IS - 10
ER -