Novel models for human scirrhous gastric carcinoma in vivo.
Human scirrhous gastric carcinoma, a diffusely infiltrating type of poorly differentiated gastric carcinoma also known as linitis plastica type carcinoma, is characterized by cancer cell infiltration and proliferation accompanied with extensive stromal fibrosis. We established two new gastric cancer cell lines, designated OUCM-8 and OCUM-11, which developed the characteristic biology of scirrhous gastric carcinoma upon orthotopic implantation in mice. Involvement of lymph nodes and liver metastasis was also found in both orthotopic models. Histologically, these orthotopic models showed proliferation with extensive fibrosis, resembling human scirrhous gastric cancer. Both cell lines were derived from ascites of patients with scirrhous gastric cancer. The growth of OCUM-8 and OCUM-11 cells following the addition of KGF, FGF, and EGF was increased significantly relative to untreated cells. An increase in the number of attached and spreading cells occurred following the addition of TGF-beta 1 in both cell lines. OCUM-11 cells showed microsatellite instability. Although subcutaneous scirrhous gastric cancer cells show medullary growth, most in vivo studies of scirrhous gastric cancer have used xenografted tumors implanted subcutaneously. Only in a few cases was it confirmed that these scirrhous gastric cancer cell lines retained the original histologic characteristics. Our orthotopic models should contribute to the elucidation of disease progression in situ and to the development of therapy for scirrhous gastric cancer.
Takemura
Satoru
S
The Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka 545-8585.
Yashiro
Masakazu
M
Sunami
Takeshi
T
Tendo
Masashige
M
Hirakawa
Kosei
K
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D043171:Chromosomal Instability; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D008039:Linitis Plastica / Q000235:genetics / Q000473:pathology; D008113:Liver Neoplasms; D019656:Loss of Heterozygosity; D008207:Lymphatic Metastasis; D051379:Mice; D008819:Mice, Nude; D018895:Microsatellite Repeats; D009154:Mutation; D009368:Neoplasm Transplantation; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology
D006133:Growth Substances