Differential expression of the human metastasis adhesion molecule CD44V in normal and carcinomatous stomach mucosa of Chinese subjects.
BACKGROUND
CD44 is a cell surface adhesion molecule involved in cell-cell and cell-matrix interactions. Tumor cells transfected to overexpress the isoform CD44V readily gain access to lymph nodes and form distant metastases.


METHODS
Monoclonal antibodies directed at epitopes common to known CD44 isoforms were used to investigate CD44V expression in 30 normal gastric mucosa tissues, 64 different gastric adenocarcinomas, 20 metastatic adenocarcinoma lymph nodes and 4 established gastric carcinoma cell lines. In addition, CD44V gene expression in six gastric adenocarcinoma tissues and four gastric cancer cell lines were investigated by northern blotting.


RESULTS
Immunohistochemistry screening of 30 subjects with normal gastric mucosa did not reveal expression of CD44 variants. Areas of intestinal metaplasia, a precancerous lesion, were stained with antibodies against either V5- or V6-containing isoforms of CD44. Tubular and signet-ring cell types of adenocarcinoma were strongly positive for epitopes encoded by CD44 variants containing exons V5 (41/49 and 10/10, respectively). Some tubular type adenocarcinomas (15/49) also expressed CD44 variants containing the V6 epitope. Tumor differentiation was closely related to CD44 V5 expression (P < 0.001). In addition, 18 of 20 gastric adenocarcinomas metastatic to lymph nodes expressed the V5 epitope of CD44 and 4 of 20 expressed the V6 epitope. Analysis of four established gastric adenocarcinoma cell lines revealed that two had moderate to strong expression of exons V5 and V6 of CD44. An antibody directed against CD44 variants containing exons V8 to V10 strongly stained all gastric adenocarcinoma cell lines. Northern blotting demonstrated that all four tumor cell lines and six gastric carcinoma mucosa tissues expressed CD44V.


CONCLUSIONS
Generation of CD44 splice variants may be closely linked with gastric carcinoma tumorigenesis and differentiation. In addition, expression of CD44 variants containing exons V5 and V6 may be used as an indicator of evolving gastric cancer.
Harn
H J
HJ
Department of Pathology, Tri-Service General Hospital, Taipei, Taiwan.
Ho
L I
LI
Chang
J Y
JY
Wu
C W
CW
Jiang
S Y
SY
Lee
H S
HS
Lee
W H
WH
D000230:Adenocarcinoma / Q000276:immunology*; D000911:Antibodies, Monoclonal; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002681:China; D000939:Epitopes; D005753:Gastric Mucosa / Q000276:immunology*; D015870:Gene Expression; D006801:Humans; D018960:Hyaluronan Receptors; D007124:Immunoenzyme Techniques; D009362:Neoplasm Metastasis; D009693:Nucleic Acid Hybridization; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D016201:Receptors, Lymphocyte Homing / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D000939:Epitopes; D018960:Hyaluronan Receptors; D011956:Receptors, Cell Surface; D016201:Receptors, Lymphocyte Homing