Down-regulation of E-cadherin by antisense oligonucleotide enhances basement membrane invasion of pancreatic carcinoma cells.
Pancreatic carcinoma shows a marked invasiveness around tissues lymph node and/or hematogenous metastases resulting in poor prognoses of the patients. We examined on whether E-cadherin is associated with these malignant behaviors of pancreatic carcinoma cells using a human pancreatic adenocarcinoma cell line, JHP-1. Immunohistochemically, E-cadherin expression of JHP-1 cells was remarkably inhibited by treatment with E-cadherin antisense oligonucleotide. By invasion-MTT assay, JHP-1 cells treated with E-cadherin antisense oligonucleotide showed a significant increase of invasiveness compared to those treated with the control oligonucleotide (P < 0.001), whereas the proliferation of JHP-1 cells was not affected by the presence of either E-cadherin antisense or control oligonucleotide. Thus, down-regulation of E-cadherin of pancreatic carcinoma cells induced the invasiveness into the basement membrane. These results suggest that the reduction in E-cadherin expression plays a key role not only in detachment of cell-cell adhesion but also in invasion and metastasis of pancreatic carcinoma cells.
First Department of Surgery, Kagoshima University School of Medicine. sonshin@med6.kufm.kagoshima-u.ac.jp
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Takao
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Che
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Fukudome
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Natsugoe
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Ozawa
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Aikou
D000230:Adenocarcinoma / Q000473:pathology*; D001485:Basement Membrane / Q000473:pathology; D015820:Cadherins / Q000378:metabolism* / Q000502:physiology; D015536:Down-Regulation; D015316:Genetic Therapy; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D020320:Oligoribonucleotides, Antisense / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
D015820:Cadherins; D020320:Oligoribonucleotides, Antisense