Heparanase expression correlates with invasion and poor prognosis in gastric cancers.
Degradation of basement membrane and extracellular matrix structures are important features of the metastatic process of malignant tumors. Human heparanase degrades heparan sulfate proteoglycans, which represent the main components of basement membranes and the extracellular matrix. Because of the role of heparanase in tumor invasion and metastasis, we examined heparanase expression in primary gastric cancers and in cell lines derived from gastric cancers by immunohistochemistry and RT-PCR, respectively. Four of seven gastric cancer cell lines showed heparanase mRNA expression by RT-PCR. Heparanase protein was detected in both the cytoplasm and the nucleus of heparanase mRNA-positive cells by immunohistochemical staining. Heparanase expression was confirmed in 35 (79.5%) of 44 gastric tumor samples by immunohistochemical staining. However, no or weak heparanase expression was detected in normal gastric mucosa. 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. Analysis of the clinicopathologic features showed stronger heparanase expression in cases of huge growing tumors, extensive invasion to lymph vessels, and regional lymph node metastasis. In gastric cancer, patients with heparanase expression showed significantly poorer prognosis than those without such expression (p = 0.006). In conclusion, our findings suggest that high expression of heparanase in gastric cancer is a strong predictor of poor survival.
Department of First Surgery, Graduate School of Medicine and Dentistry, Okayama University, Okayama, Japan.
Munenori
M
Takaoka
Yoshio
Y
Naomoto
Takaomi
T
Ohkawa
Hirokazu
H
Uetsuka
Yasuhiro
Y
Shirakawa
Futoshi
F
Uno
Toshiyoshi
T
Fujiwara
Mehmet
M
Gunduz
Hitoshi
H
Nagatsuka
Motowo
M
Nakajima
Noriaki
N
Tanaka
Minoru
M
Haisa
D000818:Animals; D005966:Glucuronidase / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D000099175:Heparanase
D005966:Glucuronidase; D012333:RNA, Messenger; D000099175:Heparanase