Advanced

Dermatan sulfate is involved in the tumorigenic properties of Esophagus Squamous Cell Carcinoma.

Thelin, Martin LU ; Svensson, Katrin LU ; Shi, Xiaofeng; Bagher, Mariam LU ; Axelsson, Jakob B LU ; Isinger Ekstrand, Anna LU ; van Kuppevelt, Toin H; Johansson, Jan LU ; Nilbert, Mef LU and Zaia, Joseph, et al. (2012) In Cancer Research 72(8). p.1943-1952
Abstract
Extracellular matrix, either produced by cancer cells or by cancer-associated fibroblasts, influences angiogenesis, invasion and metastasis. Chondroitin/dermatan sulfate (CS/DS) proteoglycans, which occur both in the matrix and at the cell surface, play important roles in these processes. The unique feature that distinguishes DS from CS is the presence of iduronic acid (IdoA) in DS. Here, we report that CS/DS is increased five-fold in human biopsies of esophagus squamous cell carcinoma (ESCC), an aggressive tumor with poor prognosis, as compared with normal tissue. The main IdoA-producing enzyme, DS epimerase 1 (DS-epi1), together with the 6-O- and 4-O-sulfotransferases, were highly up-regulated in ESCC biopsies. Importantly, CS/DS... (More)
Extracellular matrix, either produced by cancer cells or by cancer-associated fibroblasts, influences angiogenesis, invasion and metastasis. Chondroitin/dermatan sulfate (CS/DS) proteoglycans, which occur both in the matrix and at the cell surface, play important roles in these processes. The unique feature that distinguishes DS from CS is the presence of iduronic acid (IdoA) in DS. Here, we report that CS/DS is increased five-fold in human biopsies of esophagus squamous cell carcinoma (ESCC), an aggressive tumor with poor prognosis, as compared with normal tissue. The main IdoA-producing enzyme, DS epimerase 1 (DS-epi1), together with the 6-O- and 4-O-sulfotransferases, were highly up-regulated in ESCC biopsies. Importantly, CS/DS structure in patient tumors was significantly altered compared with normal tissue, as determined by sensitive mass spectrometry. To further understand the roles of IdoA in tumor development, DS-epi1 expression, and consequently IdoA content, wasdownregulated in ESCC cells. IdoA-deficient cells exhibited decreased migration and invasion capabilities in vitro, which was associated with reduced cellular binding of hepatocyte growth factor, inhibition of pERK-1/2 signaling, and de-regulated actin cytoskeleton dynamics and focal adhesion formation. Our findings demonstrate that IdoA in DS influences tumorigenesis by affecting cancer cell behavior. Therefore, down-regulation of IdoA by DS-epi1 inhibitors may represent a new anti-cancer therapy. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancer Research
volume
72
issue
8
pages
1943 - 1952
publisher
American Association for Cancer Research
external identifiers
  • WOS:000302905700006
  • PMID:22350411
  • Scopus:84860174216
ISSN
1538-7445
DOI
10.1158/0008-5472.CAN-11-1351
language
English
LU publication?
yes
id
3964f13f-3f9a-4b65-a0b0-d850e340e7d2 (old id 2366675)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22350411?dopt=Abstract
date added to LUP
2012-03-02 12:49:50
date last changed
2017-01-01 07:54:00
@article{3964f13f-3f9a-4b65-a0b0-d850e340e7d2,
  abstract     = {Extracellular matrix, either produced by cancer cells or by cancer-associated fibroblasts, influences angiogenesis, invasion and metastasis. Chondroitin/dermatan sulfate (CS/DS) proteoglycans, which occur both in the matrix and at the cell surface, play important roles in these processes. The unique feature that distinguishes DS from CS is the presence of iduronic acid (IdoA) in DS. Here, we report that CS/DS is increased five-fold in human biopsies of esophagus squamous cell carcinoma (ESCC), an aggressive tumor with poor prognosis, as compared with normal tissue. The main IdoA-producing enzyme, DS epimerase 1 (DS-epi1), together with the 6-O- and 4-O-sulfotransferases, were highly up-regulated in ESCC biopsies. Importantly, CS/DS structure in patient tumors was significantly altered compared with normal tissue, as determined by sensitive mass spectrometry. To further understand the roles of IdoA in tumor development, DS-epi1 expression, and consequently IdoA content, wasdownregulated in ESCC cells. IdoA-deficient cells exhibited decreased migration and invasion capabilities in vitro, which was associated with reduced cellular binding of hepatocyte growth factor, inhibition of pERK-1/2 signaling, and de-regulated actin cytoskeleton dynamics and focal adhesion formation. Our findings demonstrate that IdoA in DS influences tumorigenesis by affecting cancer cell behavior. Therefore, down-regulation of IdoA by DS-epi1 inhibitors may represent a new anti-cancer therapy.},
  author       = {Thelin, Martin and Svensson, Katrin and Shi, Xiaofeng and Bagher, Mariam and Axelsson, Jakob B and Isinger Ekstrand, Anna and van Kuppevelt, Toin H and Johansson, Jan and Nilbert, Mef and Zaia, Joseph and Belting, Mattias and Maccarana, Marco and Malmström, Anders},
  issn         = {1538-7445},
  language     = {eng},
  number       = {8},
  pages        = {1943--1952},
  publisher    = {American Association for Cancer Research},
  series       = {Cancer Research},
  title        = {Dermatan sulfate is involved in the tumorigenic properties of Esophagus Squamous Cell Carcinoma.},
  url          = {http://dx.doi.org/10.1158/0008-5472.CAN-11-1351},
  volume       = {72},
  year         = {2012},
}