The ectopeptidases CD10, CD13, CD26, and CD143 are upregulated in gastric cancer.
Due to their extracellular orientation, the ectopeptidases CD10, CD13, CD26, and CD143 have numerous functions, including the post-secretory processing of the neuropeptides and peptide hormones involved in the regulation of growth and differentiation in the gastrointestinal tract. We investigated the transcription and expression pattern of these four ectopeptidases in gastric carcinomas (GC), the corresponding non-neoplastic epithelium, a selection of lymph node metastases (LNM), and the MKN28, AGS, NCI-N87, KATO III gastric cancer cell lines. The gastric foveolar epithelium did not express CD10, CD13, or CD143, but the intestinal metaplasia demonstrated strong immunoreactivity at the brush border for all four ectopeptidases. CD10, CD13, and CD143 were significantly up-regulated in GCs and the lymph node metastases, confirming that they are important for the tumor cell biology. However, there is a lack of correlation between expression in intestinal metaplasia and tumor, as well as in tumor and LNM. Cell proliferation assays were performed with MKN28 and AGS, in which inhibition of CD10 significantly reduced the growth of both cell lines, and inhibition of CD13 significantly increased the proliferation of the AGS cells, indicating that the ability to degrade gastrointestinal peptides may play an important role in the pathobiology of gastric cancer.
Carl-McGrath
Stacy
S
Department of Pathology, Otto-von-Guericke University, Leipziger Strasse 44, D-39120 Magdeburg, Germany.
Lendeckel
Uwe
U
Ebert
Matthias
M
Wolter
Alexandra-Beatrice
AB
Roessner
Albert
A
Röcken
Christoph
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018826:CD13 Antigens / Q000096:biosynthesis* / Q000235:genetics; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation; D018819:Dipeptidyl Peptidase 4 / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000096:biosynthesis* / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis* / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D018826:CD13 Antigens; D018819:Dipeptidyl Peptidase 4; D007703:Peptidyl-Dipeptidase A; D015260:Neprilysin