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

Abstract

We established a new cell line, AZ-P7a, with high peritoneal-metastatic potential in nude mice. AZP7a cells were derived from the human gastric carcinoma line AZ-521, which has low capacity for peritoneal dissemination. AZ-P7a cells developed peritoneal metastasis in 11/14 (78.6%) mice, whereas the parental AZ-521 cells developed metastasis in 2/6 (33.3%) mice. The metastatic foci in the peritoneum showed essentially the same histological appearance as those induced by parental cells. The tumorigenicity and the motile activity of AZ-P7a cells were stronger than those of the parental AZ-521 cells; in contrast, adhesion to the extracellular matrix and the production of vascular endothelial growth factor by AZ-P7a cells were decreased. In fluorescence-activated cell sorter (FACS) analysis, AZ-P7a cells expressed significantly greater levels of integrins α α α α2, α α α α3, α α α α5, α α α α6 and α α α αvβ β β β5, as compared with AZ-521 cells. However, α α α α1, α α α α4, α α α αvβ β β β3, hCD44H, hCD44v3, hCD44v6 and hCD44v10 were not expressed in either cell line. AZ-P7a cells developed no liver metastasis when administered by the intrasplenic injection method, though the highly liver metastatic cell line AZ-H5c showed the same rate of peritoneal dissemination as that exhibited by AZP7a cells after intraabdominal injection. These findings suggested that the mechanism of peritoneal dissemination differed from that of hematogenous metastasis. Moreover, the latter appears to be controlled by more complex mechanisms than the former. Thus, this cell line might be useful for investigating the mechanism of peritoneal dissemination of human gastric cancer. Key words: Gastric carcinoma lines -Peritoneal dissemination model -Nude micePeritoneal dissemination is most frequently observed in human gastric cancer and is one of the most important causes of cancer deaths. Although some trials to prevent peritoneal dissemination of gastric cancer have been performed, 1) including chemotherapy, hyperthermia and peritonectomy, no effective prolongation of survival has been attained in most patients.2) The establishment of relevant animal models of metastasis is extremely important for the development of new therapeutic modalities for gastric cancer. To elucidate the molecular mechanisms of metastasis, several excellent hematogenous metastatic models have been established by intrasplenic injection [3][4][5] and the orthotopic implantation technique. [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)

Cytoreductive Surgery Followed by Hyperthermic Intraperitoneal Chemotherapy: Morbidity and Mortality Analysis of Our Patients

“…[7][8][9][10] Major morbidity and postoperative mortality of this series was 27% and 7.6% respectively; which are similar to the incidence reported by specialized centers. [8][9][10][11] The main morbidity of cytoreductive surgery combined with HIPEC is due to complications of surgery such as anastomotic leakages, intraperitoneal sepsis, or abscesses. 12 Wound infections (n= 3) and intestinal fistula (n= 2) were the most common causes of morbidity in our patients.…”

“…8 Many phase I and II studies have been conducted with promising results and this new treatment modality has gained increasingly wide acceptance in the treatment of PC. [7][8][9][10] To achieve effective cytoreduction, the area of surgery should be wide and multiple organ parts may be resected. This leads to a high risk of major postoperative complications such as digestive fistu- CT, computed tomography.…”

Prognostic factors and oncologic outcome in 146 patients with colorectal peritoneal carcinomatosis treated with cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy: Italian multicenter study S.I.T.I.L.O.

“…influences the development of secondary distant metastases and predicts survival [27,28]. An ad interim solution could be to undertake specifically designed studies to assess each of the currently used prognostic variables through multivariate analysis and to construct a scoring system of predictive variables each carrying its own specific weight.…”

Inhibitory effect of endothelin A receptor blockade on tumor growth and liver metastasis of a human gastric cancer cell line

“…In this Tokyo, Japan), and established highly metastatic variants, AZ-H5c (a liver metastatic line), AZ-P7a (a peritoneal dissemination line), and AZ-L5G (a lymph node metastatic line), were used in this study [1][2][3]. These three highly metastatic variants were established in our institution as previously described [1][2][3]; their metastatic rates are presented in Fig. 1.…”