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      A Novel Experimental Mouse Model of Peritoneal Dissemination of Human Gastric Cancer Cells: Analysis of the Mechanism of Peritoneal Dissemination Using cDNA Macroarrays

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          Abstract

          We established a new cell line, NUGC‐3P4T, with high peritoneal metastatic disseminating potential in nude mice. NUGC‐3P4T cells were derived from the human gastric carcinoma line NUGC‐3, which has low capacity for peritoneal dissemination. NUGC‐3P4T cells developed peritoneal dissemination in 10/10 (100%) mice, whereas the parental NUGC‐3 cells developed dissemination in 1/5 (20.0%) mice. The metastatic foci in the peritoneum showed essentially the same histological appearance as those induced by parental cells. The tumorigenicity, the motile activity and the adhesive activity to the laminin of NUGC‐3P4T cells were stronger than those of NUGC‐3 cells. Production of IL‐8 was significantly higher in NUGC‐3P4T than in NUGC‐3. cDNA macroarrays analysis showed that a variety of cytokines, interleukins, and other immunomodulators and their receptors were up‐ or down‐regulated at the mRNA level in NUGC‐3P4T cells, compared with NUGC‐3 cells. Thus, this unique cell line and in vivo model might be useful to study the biology of peritoneal dissemination of human gastric cancer.

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          Most cited references36

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          Models of human metastatic colon cancer in nude mice orthotopically constructed by using histologically intact patient specimens.

          There is an important need for clinically relevant animal models for human cancers. Toward this goal, histologically intact human colon-cancer specimens derived surgically from patients were implanted orthotopically to the colon or cecum of nude mice. We have observed extensive orthotopic growth in 13 of 20 cases of implanted patient colon tumors. These showed various growth patterns with subsequent regional, lymph-node, and liver metastasis, as well as general abdominal carcinomatosis. Thus, models for human colon cancer have been developed that show (i) local growth, (ii) abdominal metastasis, (iii) general abdominal carcinomatosis with extensive peritoneal seeding, (iv) lymph-node metastasis, (v) liver metastasis, and (vi) colonic obstruction. These models permit the passage of the tumors to form large cohorts. They will facilitate research into the biology of colon cancer metastatic capability and the development of new drugs active against metastatic cancer. These models may also predict the clinical course and the in vivo response to drugs of the cancer of individual patients.
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            Integrin distribution in malignant melanoma: association of the beta 3 subunit with tumor progression.

            Since tumor progression is dependent on the ability of malignant cells to interact with the extracellular matrix, molecules on the cell surface which mediate cell-substratum interactions are likely to be important regulators of tumor invasion and metastasis. The purpose of this study was to examine the distribution of one such group of cell adhesion receptors, the integrins, in benign and malignant lesions of human melanocytes. The distribution of integrin adhesion receptors was defined on cells in culture derived from normal and malignant melanocytes and in tissue sections from benign to increasingly malignant melanocytic lesions using a panel of monoclonal antibodies against specific integrin subunits. Cells in culture expressed a large variety of integrins, including all of the previously characterized members of the beta 1 subfamily plus the alpha v/beta 3 vitronectin receptor. The expression of integrins was similar in cells cultured from either benign or malignant lesions. In contrast, consistent differences were noted in integrin expression by cells within tissues containing metastatic and vertical growth phase melanomas when compared to radial growth phase melanoma cells and cells within nevi. Most notably, the expression of the beta 3 subunit was restricted exclusively to cells within vertical growth phase and metastatic melanomas. The presence of this integrin may be important in the development of tumor invasiveness and could be useful as a marker of melanoma cells entering the more aggressive phase of the malignant process.
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              Milky spots as the implantation site for malignant cells in peritoneal dissemination in mice.

              We examined the site-specific implantation of cancer cells in peritoneal tissues after an i.p. inoculation of 10(5) P388 leukemia cells. Twenty-four h after the inoculation, the number of viable cancer cells infiltrating into specific tissue sites of the peritoneum was estimated by an i.p. transfer method. A descending order of tissue implantation with cancer cells was established as omentum > gonadal fat > mesenterium > posterior abdominal wall > stomach, liver, intestine, anterior abdominal wall, and lung. A significant correlation was established between the logarithm of the number of infiltrating cancer cells and the logarithm of the number of milky spots. Next, the omentum was examined microscopically after i.p. inoculation with P388 leukemia cells labeled with bromodeoxyuridine or B-16 PC melanoma, which were differentiated from the other cells by an immunocytological method using anti-bromodeoxyuridine antibody or by the melanin of the B-16 PC melanoma cells. These cancer cells were found microscopically to be infiltrating only the milky spots, whereas none were seen at the other sites. These results suggest that cancer cells seeded i.p. specifically infiltrate the milky spots in the early stage of peritoneal metastases.
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                Author and article information

                Journal
                Jpn J Cancer Res
                Jpn. J. Cancer Res
                10.1111/(ISSN)1349-7006a
                CAS
                Japanese Journal of Cancer Research : Gann
                Blackwell Publishing Ltd (Oxford, UK )
                0910-5050
                1876-4673
                July 2001
                : 92
                : 7 ( doiID: 10.1111/cas.2001.92.issue-7 )
                : 748-754
                Affiliations
                [ 1 ]First Department of Surgery, Sapporo Medical University School of Medicine, S‐l W‐16, Chuo‐ku, Sapporo 060‐8543
                [ 2 ]First Department of Pathology, Sapporo Medical University School of Medicine, S‐l W‐16, Chuo‐ku, Sapporo 060‐8543
                [ 3 ]Department of Surgery, Koshin Hospital, 5‐5‐35 Oyachi‐higashi, Atsubetsu‐ku, Sapporo 004‐0041
                Author notes
                [*] [* ] To whom correspondence should be addressed. E‐mail: yasoshima@ 123456mtf.biglobe.ne.jp
                Article
                CAE748
                10.1111/j.1349-7006.2001.tb01157.x
                5926777
                11473725
                61872eff-6c55-4f7c-9994-2ae15eba91d3
                History
                Page count
                References: 37, Pages: 7
                Categories
                Article
                Custom metadata
                2.0
                July 2001
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.6.9 mode:remove_FC converted:04.11.2015

                gastric cancer lines,peritoneal dissemination model,nude mice,cdna macroarray

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