Dysadherin expression facilitates cell motility and metastatic potential of human pancreatic cancer cells.
Dysadherin is a membrane glycoprotein expressed strongly in several human cancers. Overexpression of dysadherin in tumor cells is closely associated with malignant phenotype (e.g., metastasis) and poor prognosis. In our analysis, six pancreatic cancer cell lines showed a positive correlation between dysadherin expression and cell motility. Introduction of small interfering RNA (siRNA) against dysadherin into the Panc-1 cell line caused reduction of dysadherin expression and suppression of cell motility. In contrast, stable transfection of a dysadherin expression vector into the Capan-1 cell line increased cell motility. In vivo, the metastatic potential of orthotopically transplanted Capan-1 tumor cells in severe combined immunodeficient mice was increased by dysadherin overexpression. Cell morphology and actin organization were also influenced by modulation of dysadherin expression. Cells transfected with dysadherin siRNA tended to have a relatively larger, more spread shape and increased transverse actin stress fibers compared with parent cells and cells transfected with control siRNA. Our study suggests that dysadherin is able to modulate actin structures, stimulate cell motility, and contribute directly to the metastatic potential of human pancreatic cancer cells.
Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.
Takeshi
T
Shimamura
Jun
J
Yasuda
Yoshinori
Y
Ino
Masahiro
M
Gotoh
Akira
A
Tsuchiya
Atsushi
A
Nakajima
Michiie
M
Sakamoto
Yae
Y
Kanai
Setsuo
S
Hirohashi
D000199:Actins / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D018076:DNA, Complementary / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007473:Ion Channels; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D016513:Mice, SCID; D008840:Microfilament Proteins; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection
D000199:Actins; D018076:DNA, Complementary; C451410:FXYD5 protein, human; D007473:Ion Channels; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering