Involvement of adhesion molecules in metastasis of SW1990, human pancreatic cancer cells.
OBJECTIVE
Peritoneal dissemination and hepatic metastasis commonly occur after patients with pancreatic cancer have undergone surgery. It is thought that specific adhesion molecules play corresponding roles in cancer metastasis.


METHODS
We conducted in vitro and in vivo studies to assess the role of adhesion molecules in these processes, using SW1990 cells derived from human pancreatic cancer.


RESULTS
SW1990 cells pronouncedly expressed sialyl Lewis(a) (s-Le[a]) and sialyl Lewis(x) antigens (s-Le[x]), CD44H, and beta1 integrin. Also, SW1990 cells showed a strong binding activity to IL-1beta activated human umbilical vein endothelial cells, cultured murine endothelial cells (F-2 cells), and human peritoneal mesothelial cells. Invasive ability of SW1990 cells to F-2 cells was also observed. The adhesion leading to implantation of cancer cells to endothelial cells were inhibited by treatment with the antibodies against s-Le(a) and against beta1 integrin, respectively. Treatments with the antibodies against s-Le(a) and beta1 integrin each inhibited the development of liver metastasis in nude mice with SW1990 cells. The adhesion of SW1990 cells to peritoneal mesothelial cells was markedly inhibited by antibodies each against CD44 or beta1 integrin, but was completely blocked by using a combination of these two antibodies. These antibodies inhibited the dissemination of SW1990 cells in the peritoneal cavity of nude mice and prolonged their survival.


CONCLUSIONS
These findings suggest that s-Le(a) and integrin mediate the process from adhesion to implantation of SW1990 cells to endothelial cells, and CD44 and integrin play important roles in the initial attachment of SW1990 cells to mesothelial cells. It is thus speculated that compounds that interfere with the function of cell adhesion molecules may decrease the incidence of pancreatic cancer metastasis.
Hosono
J
J
Department of Surgery II, Nagoya University School of Medicine, Japan.
Narita
T
T
Kimura
N
N
Sato
M
M
Nakashio
T
T
Kasai
Y
Y
Nonami
T
T
Nakao
A
A
Takagi
H
H
Kannagi
R
R
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000502:physiology*; D019040:E-Selectin / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology / Q000502:physiology; D019012:Integrin beta1 / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D016256:Lewis X Antigen / Q000276:immunology / Q000502:physiology*; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000473:pathology* / Q000628:therapy; D010534:Peritoneal Neoplasms / Q000556:secondary; D014407:Tumor Cells, Cultured
D000906:Antibodies; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D018960:Hyaluronan Receptors; D019012:Integrin beta1; D007375:Interleukin-1; D016256:Lewis X Antigen