Loss of syndecan-1 and increased expression of heparanase in invasive esophageal carcinomas

Shuji Mikami, K. Ohashi, Y. Usui, T. Nemoto, K. I. Katsube, M. Yanagishita, M. Nakajima, K. Nakamura, M. Koike

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

Heparan sulfate proteoglycans play important biological roles in cell-cell and cell-matrix adhesion, and are closely associated with growth factor actions. Loss of syndecan-1, a cell surface-bound heparan sulfate proteoglycan, has been reported for advanced head and neck carcinomas, and expression of endoglycosidic heparanase, which cleaves heparan sulfate glycosaminoglycans (HS-GAGs), is associated with invasion and metastatic potential of malignant tumors. Paraffin sections of 103 primary esophageal squamous cell carcinomas were immunohistochemically examined for the expression of syndecan-1 core protein, HS-GAGs and heparanase protein, and the results were compared with various clinicopathological parameters, such as invasion depth. For 16 cases, fresh tumor samples were quantitatively analyzed for heparanase and syndecan-1 mRNA expression by real-time RT-PCR in addition to the immunohistochemical studies. Syndecan-1 core protein and HS-GAGs expression was significantly decreased in pT2 and pT3 cases compared with their pTis and pT1 counterparts. Decreased expression of core protein and HS-GAGs was correlated with the incidence of lymphatic invasion, and venous involvement. Furthermore, decreased expression of HS-GAGs was correlated positively with the incidence of nodal metastasis and distant organ metastasis, and negatively with the grade of tumor cell differentiation. The percentage of cytoplasmic heparanase protein-positive cases increased significantly in pT2 and pT3 cases compared to that in pTis and pT1 cases, and this was associated with lymphatic invasion, and venous and lymph nodal involvement. The level of heparanase mRNA was inversely correlated with the degree of HS-GAGs expression rather than core protein. In conclusion, loss of syndecan-1 and heparanase overexpression in esophageal squamous cell carcinomas are closely associated with malignant potential. Regarding the mechanism of loss of HS-GAGs, heparanase upregulation appears to play an important role.

Original languageEnglish
Pages (from-to)1062-1073
Number of pages12
JournalJapanese Journal of Cancer Research
Volume92
Issue number10
Publication statusPublished - 2001

Fingerprint

Syndecan-1
Heparitin Sulfate
Glycosaminoglycans
Carcinoma
Heparan Sulfate Proteoglycans
Proteins
Cell-Matrix Junctions
Neoplasm Metastasis
Neoplasms
Messenger RNA
Incidence
Lymph
heparanase
Paraffin
Real-Time Polymerase Chain Reaction
Cell Differentiation
Intercellular Signaling Peptides and Proteins
Neck
Up-Regulation
Head

Keywords

  • Esophageal squamous cell carcinoma (ESCC)
  • Heparan sulfate proteoglycan (HSPG)
  • Heparanase
  • Syndecan-1

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Mikami, S., Ohashi, K., Usui, Y., Nemoto, T., Katsube, K. I., Yanagishita, M., ... Koike, M. (2001). Loss of syndecan-1 and increased expression of heparanase in invasive esophageal carcinomas. Japanese Journal of Cancer Research, 92(10), 1062-1073.

Loss of syndecan-1 and increased expression of heparanase in invasive esophageal carcinomas. / Mikami, Shuji; Ohashi, K.; Usui, Y.; Nemoto, T.; Katsube, K. I.; Yanagishita, M.; Nakajima, M.; Nakamura, K.; Koike, M.

In: Japanese Journal of Cancer Research, Vol. 92, No. 10, 2001, p. 1062-1073.

Research output: Contribution to journalArticle

Mikami, S, Ohashi, K, Usui, Y, Nemoto, T, Katsube, KI, Yanagishita, M, Nakajima, M, Nakamura, K & Koike, M 2001, 'Loss of syndecan-1 and increased expression of heparanase in invasive esophageal carcinomas', Japanese Journal of Cancer Research, vol. 92, no. 10, pp. 1062-1073.
Mikami, Shuji ; Ohashi, K. ; Usui, Y. ; Nemoto, T. ; Katsube, K. I. ; Yanagishita, M. ; Nakajima, M. ; Nakamura, K. ; Koike, M. / Loss of syndecan-1 and increased expression of heparanase in invasive esophageal carcinomas. In: Japanese Journal of Cancer Research. 2001 ; Vol. 92, No. 10. pp. 1062-1073.
@article{1371822e7a6a4038b312a920ba7ec906,
title = "Loss of syndecan-1 and increased expression of heparanase in invasive esophageal carcinomas",
abstract = "Heparan sulfate proteoglycans play important biological roles in cell-cell and cell-matrix adhesion, and are closely associated with growth factor actions. Loss of syndecan-1, a cell surface-bound heparan sulfate proteoglycan, has been reported for advanced head and neck carcinomas, and expression of endoglycosidic heparanase, which cleaves heparan sulfate glycosaminoglycans (HS-GAGs), is associated with invasion and metastatic potential of malignant tumors. Paraffin sections of 103 primary esophageal squamous cell carcinomas were immunohistochemically examined for the expression of syndecan-1 core protein, HS-GAGs and heparanase protein, and the results were compared with various clinicopathological parameters, such as invasion depth. For 16 cases, fresh tumor samples were quantitatively analyzed for heparanase and syndecan-1 mRNA expression by real-time RT-PCR in addition to the immunohistochemical studies. Syndecan-1 core protein and HS-GAGs expression was significantly decreased in pT2 and pT3 cases compared with their pTis and pT1 counterparts. Decreased expression of core protein and HS-GAGs was correlated with the incidence of lymphatic invasion, and venous involvement. Furthermore, decreased expression of HS-GAGs was correlated positively with the incidence of nodal metastasis and distant organ metastasis, and negatively with the grade of tumor cell differentiation. The percentage of cytoplasmic heparanase protein-positive cases increased significantly in pT2 and pT3 cases compared to that in pTis and pT1 cases, and this was associated with lymphatic invasion, and venous and lymph nodal involvement. The level of heparanase mRNA was inversely correlated with the degree of HS-GAGs expression rather than core protein. In conclusion, loss of syndecan-1 and heparanase overexpression in esophageal squamous cell carcinomas are closely associated with malignant potential. Regarding the mechanism of loss of HS-GAGs, heparanase upregulation appears to play an important role.",
keywords = "Esophageal squamous cell carcinoma (ESCC), Heparan sulfate proteoglycan (HSPG), Heparanase, Syndecan-1",
author = "Shuji Mikami and K. Ohashi and Y. Usui and T. Nemoto and Katsube, {K. I.} and M. Yanagishita and M. Nakajima and K. Nakamura and M. Koike",
year = "2001",
language = "English",
volume = "92",
pages = "1062--1073",
journal = "Cancer Science",
issn = "1347-9032",
publisher = "Wiley-Blackwell",
number = "10",

}

TY - JOUR

T1 - Loss of syndecan-1 and increased expression of heparanase in invasive esophageal carcinomas

AU - Mikami, Shuji

AU - Ohashi, K.

AU - Usui, Y.

AU - Nemoto, T.

AU - Katsube, K. I.

AU - Yanagishita, M.

AU - Nakajima, M.

AU - Nakamura, K.

AU - Koike, M.

PY - 2001

Y1 - 2001

N2 - Heparan sulfate proteoglycans play important biological roles in cell-cell and cell-matrix adhesion, and are closely associated with growth factor actions. Loss of syndecan-1, a cell surface-bound heparan sulfate proteoglycan, has been reported for advanced head and neck carcinomas, and expression of endoglycosidic heparanase, which cleaves heparan sulfate glycosaminoglycans (HS-GAGs), is associated with invasion and metastatic potential of malignant tumors. Paraffin sections of 103 primary esophageal squamous cell carcinomas were immunohistochemically examined for the expression of syndecan-1 core protein, HS-GAGs and heparanase protein, and the results were compared with various clinicopathological parameters, such as invasion depth. For 16 cases, fresh tumor samples were quantitatively analyzed for heparanase and syndecan-1 mRNA expression by real-time RT-PCR in addition to the immunohistochemical studies. Syndecan-1 core protein and HS-GAGs expression was significantly decreased in pT2 and pT3 cases compared with their pTis and pT1 counterparts. Decreased expression of core protein and HS-GAGs was correlated with the incidence of lymphatic invasion, and venous involvement. Furthermore, decreased expression of HS-GAGs was correlated positively with the incidence of nodal metastasis and distant organ metastasis, and negatively with the grade of tumor cell differentiation. The percentage of cytoplasmic heparanase protein-positive cases increased significantly in pT2 and pT3 cases compared to that in pTis and pT1 cases, and this was associated with lymphatic invasion, and venous and lymph nodal involvement. The level of heparanase mRNA was inversely correlated with the degree of HS-GAGs expression rather than core protein. In conclusion, loss of syndecan-1 and heparanase overexpression in esophageal squamous cell carcinomas are closely associated with malignant potential. Regarding the mechanism of loss of HS-GAGs, heparanase upregulation appears to play an important role.

AB - Heparan sulfate proteoglycans play important biological roles in cell-cell and cell-matrix adhesion, and are closely associated with growth factor actions. Loss of syndecan-1, a cell surface-bound heparan sulfate proteoglycan, has been reported for advanced head and neck carcinomas, and expression of endoglycosidic heparanase, which cleaves heparan sulfate glycosaminoglycans (HS-GAGs), is associated with invasion and metastatic potential of malignant tumors. Paraffin sections of 103 primary esophageal squamous cell carcinomas were immunohistochemically examined for the expression of syndecan-1 core protein, HS-GAGs and heparanase protein, and the results were compared with various clinicopathological parameters, such as invasion depth. For 16 cases, fresh tumor samples were quantitatively analyzed for heparanase and syndecan-1 mRNA expression by real-time RT-PCR in addition to the immunohistochemical studies. Syndecan-1 core protein and HS-GAGs expression was significantly decreased in pT2 and pT3 cases compared with their pTis and pT1 counterparts. Decreased expression of core protein and HS-GAGs was correlated with the incidence of lymphatic invasion, and venous involvement. Furthermore, decreased expression of HS-GAGs was correlated positively with the incidence of nodal metastasis and distant organ metastasis, and negatively with the grade of tumor cell differentiation. The percentage of cytoplasmic heparanase protein-positive cases increased significantly in pT2 and pT3 cases compared to that in pTis and pT1 cases, and this was associated with lymphatic invasion, and venous and lymph nodal involvement. The level of heparanase mRNA was inversely correlated with the degree of HS-GAGs expression rather than core protein. In conclusion, loss of syndecan-1 and heparanase overexpression in esophageal squamous cell carcinomas are closely associated with malignant potential. Regarding the mechanism of loss of HS-GAGs, heparanase upregulation appears to play an important role.

KW - Esophageal squamous cell carcinoma (ESCC)

KW - Heparan sulfate proteoglycan (HSPG)

KW - Heparanase

KW - Syndecan-1

UR - http://www.scopus.com/inward/record.url?scp=0034764665&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034764665&partnerID=8YFLogxK

M3 - Article

C2 - 11676857

AN - SCOPUS:0034764665

VL - 92

SP - 1062

EP - 1073

JO - Cancer Science

JF - Cancer Science

SN - 1347-9032

IS - 10

ER -