EMAIL THIS PAGE TO A FRIEND

Clinical cancer research : an official journal of the American Association for Cancer Research

CD44 expression denotes a subpopulation of gastric cancer cells in which Hedgehog signaling promotes chemotherapy resistance.


PMID 24947926

Abstract

Gastric cancers may harbor a subset of cells with cancer stem cell (CSC) properties, including chemotherapy resistance, and CD44 is a gastric CSC marker. The Hedgehog (HH) pathway is a key developmental pathway that can be subverted by CSCs during tumorigenesis. Here, we examine the role of HH signaling in CD44(+) gastric cancer cells. Gastric cancer cell lines, tumor xenografts, and patient tumors were examined. Gastric cancer cell lines AGS, MKN-45, and NCI-N87 grown as spheroids or sorted for CD44(+) were found to have upregulation of HH pathway proteins. HH inhibition using Smoothened (Smo) shRNA or vismodegib (VIS) decreased spheroid formation and colony formation. CD44(+) cells, compared with unselected cells, were also resistant to 5-fluorouracil and cisplatin chemotherapy, and this resistance was reversed in vitro and in xenografts with Smo shRNA or VIS. CD44(+) cells also had significantly more migration, invasion, and anchorage-independent growth, and these properties could all be blocked with HH inhibition. Clinical tumor samples from a phase II trial of chemotherapy with or without VIS for advanced gastric cancer were analyzed for CD44 expression. In the chemotherapy alone group, high CD44 expression was associated with decreased survival, whereas in the chemotherapy plus VIS group, high CD44 expression was associated with improved survival. HH signaling maintains CSC phenotypes and malignant transformation phenotypes in CD44(+) gastric cancer cells, and HH inhibition can reverse chemotherapy resistance in CD44(+) cells. Gastric cancer is a heterogeneous disease, and the strategy of combining chemotherapy with HH inhibition may only be effective in tumors with high CD44 levels.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

AV44235
Anti-SHH antibody produced in rabbit, affinity isolated antibody
S8321
Anti-Sonic Hedgehog antibody, Mouse monoclonal, clone SH154, purified from hybridoma cell culture
SAB2701800
Anti-sox2 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
S9072 Anti-SOX2 antibody produced in rabbit, ~1 mg/mL, affinity isolated antibody, buffered aqueous solution
AV38232
Anti-SOX2 antibody produced in rabbit, IgG fraction of antiserum
SAB3500363
Anti-SOX2 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
SAB2104660
Anti-SOX2 antibody produced in rabbit, affinity isolated antibody
SAB4300669
Anti-SOX2 antibody produced in rabbit, affinity isolated antibody
SAB2701973
Anti-SOX2 antibody produced in rabbit
SAB2701974
Anti-SOX2 antibody produced in rabbit
SAB2103958
Anti-SOX2, (N-terminal) antibody produced in rabbit, affinity isolated antibody
C2210000
Cisplatin, European Pharmacopoeia (EP) Reference Standard
H6Cl2N2Pt
Y0001018
Cisplatin impurity A, European Pharmacopoeia (EP) Reference Standard
H6Cl2N2Pt
EHU119381 MISSION® esiRNA, esiRNA human SMO (esiRNA1)
WH0006469M3
Monoclonal Anti-SHH antibody produced in mouse, clone 1B11, purified immunoglobulin, buffered aqueous solution
S4944 Monoclonal Anti-Sonic Hedgehog (N-terminal) antibody produced in rat, clone 171018, purified immunoglobulin, lyophilized powder
S1451
Monoclonal Anti-Sox2 antibody produced in mouse, ~1.0 mg/mL, clone SOX2-6, purified immunoglobulin, buffered aqueous solution
SAB5300177
Monoclonal Anti-SOX2 antibody produced in mouse, clone 10F10, ascites fluid
SAB5300369 Monoclonal Anti-SOX2 antibody produced in mouse, clone 10F10C9, ascites fluid
1672803
Transplatin, United States Pharmacopeia (USP) Reference Standard
H6Cl2N2Pt