Expression of transforming growth factor β (TGF-β) may contribute, in part, to the variations in histogenesis and the prevalence of peritoneal dissemination in human gastric carcinoma

Niki, Masami; Toyoda, Masao; Nomura, Eiji; Shinohara, Hisashi; Nakamura, Motoyuki; Nishiguchi, Kanji; Tanigawa, Nobuhiko

doi:10.1007/pl00011716

Cited by 10 publications

(7 citation statements)

References 21 publications

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“…Transforming growth factor-b is produced not only by scirrhous gastric cancer cells (Yoshida et al, 1989;Niki et al, 2000) but also by cancer-associated fibroblasts (Mizoi et al, 1993;Inoue et al, 1997;Zeisberg et al, 2007). Our preliminary study recognised that both scirrhous gastric cancer cell lines and gastric fibroblasts produced TGF-b (Yashiro et al, 1996b;Inoue et al, 1997).…”

Section: Discussionmentioning

confidence: 56%

Inhibitory effect of a TGFβ receptor type-I inhibitor, Ki26894, on invasiveness of scirrhous gastric cancer cells

et al. 2010

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BACKGROUND: Gastric cancer cells frequently metastasise, partly because of their highly invasive nature. Transforming growth factor-b (TGF-b) receptor signalling is closely associated with the invasion of cancer cells. The aim of this study was to clarify the effect of a TGF-b receptor (TbR) phosphorylation inhibitor on the invasiveness of gastric cancer cells. METHODS: Four gastric cancer cell lines, including two scirrhous-type cell lines and two non-scirrhous-type cell lines, were used. A TbR type I (TbR-I) kinase inhibitor, Ki26894, inhibits the phosphorylation of Smad2 at an ATP-binding site of TbR-I. We investigated the expression levels of TbR and phospho-Smad2, and the effects of TGF-b in the presence or absence of Ki26894 on Smad2 phosphorylation, invasion, migration, epithelial-to-mesenchymal transition (EMT), Ras homologue gene family member A (RhoA), ZO-2, myosin, and E-cadherin expression of gastric cancer cells. RESULTS: TbR-I, TbR-II, and phospho-Smad2 expressions were found in scirrhous gastric cancer cells, but not in non-scirrhous gastric cancer cells. Ki26894 decreased Smad2 phosphorylation induced by TGF-b1 in scirrhous gastric cancer cells. Transforming growth factor-b1 upregulated the invasion, migration, and EMT ability of scirrhous gastric cancer cells. Transforming growth factor-b1 significantly upregulated the activity of RhoA and myosin phosphorylation, whereas TGF-b1 decreased ZO-2 and E-cadherin expression in scirrhous gastric cancer cells. Interestingly, Ki26894 inhibited these characteristics in scirrhous gastric cancer cells. In contrast, non-scirrhous gastric cancer cells were not affected by TGF-b1 or Ki26894 treatment. CONCLUSION: A TbR-I kinase inhibitor decreases the invasiveness and EMT of scirrhous gastric cancer cells. Ki26894 is therefore considered to be a promising therapeutic compound for the metastasis of scirrhous gastric carcinoma.

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Section: Discussionmentioning

confidence: 56%

Inhibitory effect of a TGFβ receptor type-I inhibitor, Ki26894, on invasiveness of scirrhous gastric cancer cells

et al. 2010

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“…Some neoplastic cells of the present case reacted to vimentin, suggestive of immature nature of neoplastic epithelial cells. Recently, it has been reported that desmoplasia seen in scirrhous carcinomas in the salivary gland and stomach is formed by myofibroblasts; the cells may be induced by transforming growth factor-1 produced by neoplastic cells [11]. Desmoplasia, a characteristic of the present tumor, might be induced by the same mechanisms, because many -SMA-positive myofibroblasts were seen in the desmoplastic areas.…”

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confidence: 69%

Uterine Adenocarcinoma with Prominent Desmoplasia in a Geriatric Miniature Pig

et al. 2010

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ABSTRACT. A 10-year-old miniature sow was died, showing inappetence and weight loss. Grossly, neoplastic enlargement of the uterus was found. Histopathologically, the lesions consisted of acinar, ductular and cystic proliferations of mono-and multilayered epithelial cells; these cells reacted immunohistochemically strongly with three different cytokeratin antibodies, and occasionally to vimentin. Myofibroblastic desmoplastic cells, positive to -smooth muscle actin, were present among neoplastic cells. Metastatic lesions were seen in the lungs and liver. Based on these findings, a diagnosis of uterine adenocarcinoma with marked desmoplasia was made. This case is the second report of uterine adenocarcinoma in the miniature pig. Uterine adenocarcinomas are uncommon neoplasms in most animals with the exception in rabbits and cattle [6,13]. Woman cases are the most common invasive cancers of the genital tract [3]. To our knowledge, there are two cases of uterine adenocarcinomas reported in English so far in sow; a 3-year-old crossbred Chester White-Hampshire-Duroc sow without metastases [15], and a 16-year-old Vietnamese pot-bellied pig with visceral metastases [5]. Detailed pathological examinations such as immunohistochemistry were not made for these cases. We encountered a sow bearing a uterine adenocarcinoma. Because uterine adenocarcinoma is extremely rare in sow [15], in the present study we examined histopathological and immunohistochemical characteristics of this case.

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“…72 Autocrine or paracrine production of TGF-1 by gastric cancer cells changes the morphology of mesothelial cells and may thus enhance peritoneal dissemination. [73][74][75] As elevated serum level of TGF-1 was significantly correlated with lymph node metastasis and poor prognosis, the serum level of TGF-1 might be a useful marker for predicting recurrence. 76 Type II TGF-receptor expression also correlates with progression and invasiveness of gastric cancer.…”

Section: Stomachmentioning

confidence: 98%