Establishment and Characterization of Human Gastric Carcinoma Lines with High Metastatic Potential in the Liver: Changes in Integrin Expression Associated with the Ability to Metastasize in the Liver of Nude Mice

Abstract

There is a need to establish animal models which are suitable for investigation of human gastric cancer metastasis to the liver. To this end, a human gastric carcinoma line, AZ521 was injected into the spleens of nude mice. Cells from the few liver metastatic foci of injected AZ521 were expanded in vitro and subsequently injected into the spleens of nude mice. By repeating these procedures three times, we were able to obtain a cell line, designated as AZ‐M3c, with high metastatic potential in nude mice. Liver metastasis developed in 15 of 21 (71%) animals injected with AZ‐H3c, but in only 14% of those injected with parental AZ521. Further, AZ‐H3c caused faster tumor development than did AZ521. However, the primary AZ‐H3c tumors and liver metastatic AZ‐H3c tumors showed essentially the same histological appearance. We also analyzed the cell surface expression of adhesion molecules. The data showed that the expression of VLA‐1, VLA‐2, VLA‐3, VLA‐4, VLA‐5 was enhanced in AZ‐H3c. In contrast, the expression of VLA‐6, αvβ3, E‐cadherin, ICAM‐1 and LFA‐1 was reduced in this high‐metastatic line. These results suggest that β1 mtegrins play an important role in the liver metastasis of human gastric carcinoma cells. Our high‐metastatic line should be useful for studies aimed at the prevention of liver metastasis.

Circulating intercellular adhesion molecule-1 and E-selectin levels in gastric cancer

“…Ura et al ( 1996), in contrast to our study, demonstrated that the expression of ICAM-1 was inversely correlated with liver metastasis. Yasoshima et al (1996) also showed a reduced expression of ICAM-I and of LFA-1 and increased surface expression of P1 integrins in an experimental animal model of high-metastatic gastric cancer cell line.…”

Syntenin is overexpressed and promotes cell migration in metastatic human breast and gastric cancer cell lines

“…We examined the expression of syntenin mRNA and protein in various gastric cancer cell lines (Figure 1b). Expression of syntenin mRNA and protein was elevated in SNU-5, -216, -620 and -638 cells, which are established from secondary tumor sites and metastatic (Park et al, 1990(Park et al, , 1997, compared with SNU-1, -484 and Az-521 cells, which are from the primary tumor and poorly metastatic (Park et al, 1990(Park et al, , 1997Yasoshima et al, 1996). Also, we analysed the mRNA expression of syntenin in gastric tumor tissues by Northern blot analysis (Figure 1c).…”

A Novel Experimental Mouse Model of Peritoneal Dissemination of Human Gastric Cancer Cells: Different Mechanisms in Peritoneal Dissemination and Hematogenous Metastasis

“…AZ-H5c is a highly liver metastatic cell line derived from AZ-521, and was previously reported. 9,10) The cell line was maintained in RPMI 1640 medium supplemented with 10% fetal calf serum (FCS) (Sigma, St. Louis, MO), 2 ml L-glutamine, 50 units/ml penicillin and 50 mg/ml streptomycin (Gibco, Grand Island, NY) in a humidified atmosphere of 95% air and 5% CO 2 at 37°C. The cells were passaged and expanded by trypsinization of cell monolayers followed by replating every 4-5 days.…”

“…[6][7][8] We also established and reported a highly liver metastatic cell line, AZ-H5c, derived from a human gastric cancer line, AZ-521. 9,10) …”

“…[6][7][8] We also established and reported a highly liver metastatic cell line, AZ-H5c, derived from a human gastric cancer line, AZ-521. 9,10) However, only a few peritoneal dissemination models have been reported for human gastric cancer. 11) In this study, we established a new cell line, designated as AZ-P7a, with a high potential of peritoneal dissemination in nude mice.…”