Transforming growth factor β 1 secreted from scirrhous gastric cancer cells is associated with excess collagen deposition in the tissue

Mahara, Katsuo; Kato, Junji; Terui, Takeshi; Takimoto, Rishu; Horimoto, Masayoshi; Murakami, T.; Mogi, Yoshihiro; Watanabe, Naoko; Kohgo, Yutaka; Niitsu, Yoshiro

doi:10.1038/bjc.1994.147

Cited by 52 publications

(38 citation statements)

References 19 publications

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“…The expression of TGF-b in pancreatic cancer tissue was actually 3.5-fold higher than that found in normal pancreatic regions ( Figure 1B). These results correlate with that of Friess et al (1993) types by immunohistochemistry, Northern blot analysis and/or in situ hybridisation (Samuels et al, 1989;Yoshida et al, 1989;BarrettLee et al, 1990;Gorsch et al, 1992;Walker and Dearing, 1992;Mahara et al, 1994), although none of these methods were quantitative. Our results extend these earlier studies by providing independent, quantitative analysis of the overexpression of TGF-b in pancreatic cancer by employing real-time RT -PCR methods.…”

Section: Discussionsupporting

confidence: 62%

Overexpression of TGF-β by infiltrated granulocytes correlates with the expression of collagen mRNA in pancreatic cancer

et al. 2004

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Pancreatic cancer is often associated with an intense production of interstitial collagens, known as the desmoplastic reaction. To understand more about desmoplasia in pancreatic cancer, the expression of mRNA for type I and III collagens and potent desmoplastic inducing growth factors transforming growth factor-b (TGF-b), connective tissue growth factor (CTGF), acidic and basic fibroblast growth factor (FGF), platelet-derived growth factor (PDGF) A and C and epidermal growth factor (EGF) was analysed by quantitative RT-PCR. Expression of both collagens in 23 frozen primary pancreatic cancer nodules was significantly higher than that in 15 nonneoplastic pancreatic tissues. The expressions of mRNAs for TGF-b, acidic FGF, basic FGF and PDGF C were likewise higher in surgical cancer nodules, while that of CTGF, PDGF A and EGF were not. Among these growth factors, the expression of TGF-b mRNA showed the most significant correlation with that of collagens (Po0.0001). By immunohistochemistry, TGF-b showed faint cytoplasmic staining in cancer cells. In contrast, isolated cells, mainly located on the invasive front surrounding cancerous nests, were prominently and strongly stained. These TGF-b-positive cells contained a segmented nucleus, were negative for anti-macrophage (CD68) and positive for anti-granulocyte antibodies, indicating their granulocytic nature. In conclusion, TGF-b seemed to play a major role among the various growth factors in characteristic overproduction of collagens in pancreatic cancer. Moreover, the predominant cells that express TGF-b were likely to be infiltrated granulocytes (mostly are neutrophils) and not pancreatic cancer cells.

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Section: Discussionsupporting

confidence: 62%

Overexpression of TGF-β by infiltrated granulocytes correlates with the expression of collagen mRNA in pancreatic cancer

et al. 2004

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“…TGFβ from scirrhous gastric cancer cells stimulates the proliferation of fibroblasts. Tumor cells in scirrhous carcinoma produce more TGFβ that is key mediators of fibroblast activation, than non-scirrhous carcinoma [18,19]. This different interaction between the two cell types and stromal cells is associated with the different biologic behaviors between the diffuse-type and intestinal-type in gastric carcinoma.…”

Section: Tgfβ From Gastric Cancer Cells Stimulates the Proliferation mentioning

confidence: 99%

“…TGFβ produced from fibroblasts increases the invasiveness of scirrhous gastric cancer cells [24]. TGFβ is detected in a latent form in the conditioned medium from fibroblasts and in an active form in the conditioned medium from gastric cancer cells [18,24]. The latent TGFβ is activated by proteases such as plasmin and cathepsin [25].…”

Section: Migration-stimulating Activity Of Gastric Cancer Cells By Fimentioning

confidence: 99%

Cancer–Stromal Interactions in Scirrhous Gastric Carcinoma

Yashiro

Hirakawa

2010

Cancer Microenvironment

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Fibroblasts play an important role in the progression, growth and spread of gastric cancers. Cancer-stroma interactions have been especially evident in the scirrhous type of gastric carcinoma. Fibroblasts are associated with the cancer progression at the primary and metastatic site. The proliferative and invasive ability of scirrhous gastric cancer cells are closely associated with the growth factors produced by organ-specific fibroblasts. Fibroblasts are therefore a key determinant in the malignant progression of gastric cancer and represent an important target for cancer therapies.

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“…18 Transforming growth factor-␤ (TGF-␤) activates the type I collagen genes, as well as collagen production in vitro and in vivo, 19,20 and has been ascribed to be involved in the formation of tumor desmoplasia, e.g., in scirrhous gastric cancer. 11 In a previous study, we presented evidence that stromal fibroblasts were the main producers of collagen type I in human anaplastic thyroid carcinoma. 9 Furthermore, we presented morphologic data suggesting that carcinoma cells regulate this production, possibly by augmenting translation of procollagen type I mRNAs in areas of contact between stromal and carcinoma cells.…”

mentioning

confidence: 94%

Collagen type I expression in experimental anaplastic thyroid carcinoma: Regulation and relevance for tumorigenicity

Dahlman

Lammerts

Bergström

et al. 2001

Intl Journal of Cancer

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Fibrosis in solid malignancies plays a significant role in tumor pathophysiology. Potential mechanisms for collagen type I deposition in anaplastic thyroid carcinoma (ATC) were investigated using 6 characterized ATC cell lines. Three of these cell lines, which produced collagen type I, had, as a group, a poor tumorigenicity when inoculated in athymic mice. This group of cells generated tumors in 4 of 24 injected animals (17%). Pro-␣1(I) collagen mRNA-expressing carcinoma and stromal cells were interdispersed in the tumors generated by these ATC cells. By contrast, the 3 noncollagen-producing ATC cell lines were all tumorigenic with a tumor take of 60% in the whole group. In the latter tumors, pro-␣1(I) collagen mRNA-expressing cells were confined to the stromal compartment, well delineated from carcinoma cell islets. To study the influence of ATC cells on collagen type I synthesis by fibroblasts, we used AG 1518 diploid human fibroblasts cultured on poly-(2-hydroxyethyl methacrylate) (poly[HEMA])-coated plates. This culture condition allows the study of the effect of collagen mRNA translation in the regulation of collagen type I synthesis. Conditioned media from the 6 ATC cell lines did not influence collagen synthesis. The ATC cell line KAT-4 stimulated fibroblast synthesis of collagen type I when the two cell types were cocultured on poly[HEMA]-coated substrates. Specific inhibitors of PDGF and TGF-␤ reduced the KAT 4 carcinoma cell-induced stimulation of collagen type I synthesis. Our data suggest that collagen type I production by carcinoma cells correlates negatively with tumorigenicity and that the formation of a well-defined stroma is of importance for tumor growth. Furthermore, our data suggest that tumor cells are able to stimulate collagen mRNA translation in stromal fibroblasts in direct cell-cell contact by, at least in part, transferring PDGF or TGF-␤.

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Transforming growth factor β 1 secreted from scirrhous gastric cancer cells is associated with excess collagen deposition in the tissue

Cited by 52 publications

References 19 publications

Overexpression of TGF-β by infiltrated granulocytes correlates with the expression of collagen mRNA in pancreatic cancer

Overexpression of TGF-β by infiltrated granulocytes correlates with the expression of collagen mRNA in pancreatic cancer

Cancer–Stromal Interactions in Scirrhous Gastric Carcinoma

Collagen type I expression in experimental anaplastic thyroid carcinoma: Regulation and relevance for tumorigenicity

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