Establishment of two cell lines from human gastric scirrhous carcinoma that possess the potential to metastasize spontaneously in nude mice

Abstract

lthough gastric carcinoma has recently shown a gradual decrease in prevalence, it still accounts for a significant proportion of cancer-related deaths in Japan. To improve the cure rate, more attention should be directed to early detection and prevention of metastasis of this cancer. Scirrhous carcinoma of the stomach, known as diffusely infiltrative carcinoma or Borrmann's type-IV carcinoma, or linitis plastica-type carcinoma, is characterized clinically as having the worst prognosis among the various types of gastric cancer, because it is frequently associated with metastases to lymph nodes and peritoneal dissemination. However, the mechanisms underlying this propensity for metastasis are not yet clearly understood. Therefore, establishment of relevant animal models of metastasis is considered to be extremely important for the elucidation of these mechanisms and establishment of appropriate therapeutic approaches. Transplants of human tumors into nude mice have been used increasingly as experimental systems for this purpose.1) Many human tumors can proliferate when injected s.c. into nude mice, but metastasis from the site of injection is rare.2) It has been found that in most models of human cancers, including gastric carcinoma, i.v. or intrasplenic injection, or orthotopic implantation of the tumor cells is necessary to generate metastasis. [3][4][5][6] There are few reports of spontaneous metastasis from human gastric tumor xenografts in nude mice. 7,8) To date, only one experimental model of signet-ring cell or scirrhous carcinoma of the stomach has been reported. 9) In order to address this problem, we previously established and characterized four cell lines from a primary gastric carcinoma and disseminated metastatic lesions of gastric scirrhous carcinoma.10-12) These cell lines did not exhibit the potential to form experimental or spontaneous metastases when injected s.c. or i.v., or implanted orthotopically into nude mice.We now report the establishment and the biological characterization of new human signet-ring cell gastric carcinoma cell lines that exhibit the ability to metastasize spontaneously in nude mice. Materials and MethodsOrigin and establishment of the cell lines. The HSC-44PE cell line was established from the pleural fluid, obtained by thoracocentesis, of a 28-year-old female Japanese patient with scirrhous gastric carcinoma (linitis plastica-type). The previously reported 12) and the HSC-44PE cells reported in this paper, were derived from the same patient. The former was derived from the ascitic fluid in the early stage of scirrhous gastric carcinoma, while the latter was established by culture of tumor cells collected from the pleural fluid in the terminal stage of the cancer. The HSC-58 cell line was established from the ascitic fluid, obtained by peritoneocentesis, of a 57-year-old male Japanese patient with scirrhous gastric carcinoma. The HSC-60 cell line was established from the ascitic fluid, obtained by peritoneocentesis, of a 40-year-old male patient with scirrhous gastric car...

GASDERMIN, suppressed frequently in gastric cancer, is a target of LMO1 in TGF-β-dependent apoptotic signalling

“…We used three cell lines derived from intestinal type gastric cancer, HSC57, MKN28 and MKN74 (Sekiguchi and Suzuki, 1994;Yanagihara et al, 2004), and eight cell lines derived from the diffuse type of gastric cancer cell lines, HSC39, HSC43, HSC44, HCS58, HSC59, HSC60, OCUM2M and KATO III (Sekiguchi et al, 1978;Fujihara et al, 1998;Yanagihara et al, 2004). All the cell lines were maintained in Dulbecco's modified Eagle medium (Invitrogene, Carlsbad, CA, USA).…”

Direct cancer–stromal interaction increases fibroblast proliferation and enhances invasive properties of scirrhous-type gastric carcinoma cells

“…To examine the possible effect of soluble factors in the culture media, NF-25 fibroblasts and HSC-39 cells were separately co-maintained using a 1-mm pore-sized Boyden Chamber inserts; however, no significant increase of cell proliferation was detected ( Figure 1B). Yanagihara et al (2004) previously reported that orthotopic implantation of HSC-44PE SGC cells caused a xenograft to develop in the stomach, showing extensive fibrosis with only sparse tumour cell infiltration; however, such proliferation of fibroblasts was not observed in metastatic sites including the skin, lymph node and lung, suggesting that the phenomenon is orthotopic. Thus, we next evaluated the proliferative activity of NF-j2 intestinal fibroblasts to examine whether the effect of co-culture with HSC-39 cells is tissue specific or not.…”

ZD6474 inhibits tumor growth and intraperitoneal dissemination in a highly metastatic orthotopic gastric cancer model

“…16,17 58As1 and 44As3 and human non-small cell lung cancer cell line PC-9 were maintained in RPMI-1640 medium (Sigma, St. Louis, MO) supplemented with 10% heat-inactivated FBS (Gibco BRL, Grand Island, NY). The PC-9 cells were a gift of Tokyo Medical University.…”