Expression of Scatter Factor in Human Bladder Carcinoma

Joseph, Ansamma; Weiss, Gary H.; Jin, Liang; Fuchs, Alexander; Chowdhury, Soheli A.; O'Shaugnessy, Patrick; Goldberg, Itzhak D.; Rosen, Eliot M.

doi:10.1093/jnci/87.5.372

Cited by 100 publications

(57 citation statements)

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“…We further assumed that HGF derived from tumor stroma or adjacent normal tissue might interact with the c-Met receptor on neuroblastoma cells in a paracrine manner thereby stimulating tumor invasion. This is supported by reports suggesting that the stroma from various tumors of adults contains substantial amounts of HGF (43,44).…”

Section: Discussionsupporting

confidence: 62%

Hepatocyte Growth Factor/c-Met Signaling Promotes the Progression of Experimental Human Neuroblastomas

et al. 2004

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Neuroblastoma is the most frequent solid childhood malignancy. Despite aggressive therapy, mortality is high due to rapid tumor progression to advanced stages. The molecules and mechanisms underlying poor prognosis are not well understood. Here, we report that cultured human neuroblastoma cells express the hepatocyte growth factor (HGF) and its receptor c-Met. Binding of HGF to c-Met triggers receptor autophosphorylation, indicating functional relevance of this interaction. HGF activates several downstream effectors of c-Met such as the mitogen-activated protein kinases extracellular signal-regulated kinase 1/extracellular signal-regulated kinase 2 and phospholipase C-␥, whereas signal transducer and activator of transcription 3 is constitutively activated in neuroblastoma cells expressing c-Met. In addition, HGF is able to stimulate expression and proteolytic activity of matrix metalloproteinase-2 and tissue-type plasminogen activator in neuroblastoma cells, thereby promoting degradation of extracellular matrix components. We show that HGF stimulates invasion of neuroblastoma cells in vitro and in vivo, and it promotes the formation of angiogenic neuroblastomas in vivo. These processes can be blocked by specific inhibitors of the mitogen-activated protein kinase cascade, by inhibitors of phospholipase C-␥, and also by the expression of a dominant negative signal transducer and activator of transcription 3 mutant. Our data provide the first evidence that the HGF/c-Met pathway is essential for invasiveness and malignant progression of human neuroblastomas. They further suggest that specific inhibitors of this pathway may be suitable as therapeutic agents to improve clinical outcome of neuroblastomas.

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Section: Discussionsupporting

confidence: 62%

Hepatocyte Growth Factor/c-Met Signaling Promotes the Progression of Experimental Human Neuroblastomas

et al. 2004

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“…For the determination of sRIII level in the xenograft tumors, tumor tissues were extracted as described previously (Joseph et al, 1995) with some modi®cations. Brie¯y, frozen tumor tissues were weighed, pulverized while frozen in liquid nitrogen, and extracted with ice-cold extraction bu er, 20 mM Tris, pH 7.5, 0.5 M NaCl, 0.1 mM phenylmethylsulphonyl¯uoride, at a ratio of 6 ml extraction bu er to 1 g of tissue.…”

Section: Measurement Of Sriii In the Conditioned Medium And Tumor Extmentioning

confidence: 99%

Extracellular domain of TGFβ type III receptor inhibits angiogenesis and tumor growth in human cancer cells

et al. 2002

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TGFb overexpression in human cancer cells has been shown to promote tumor progression. In the present study, we sought to determine whether sequestration of endogenous TGFb by the expression of a soluble TGFb type III receptor (sRIII), can reduce malignancy in human carcinoma cells and whether the tumor-suppressive activity of sRIII is associated with the inhibition of angiogenesis. Ectopic expression of sRIII signi®cantly inhibited the growth of tumors formed by human colon carcinoma HCT116 and breast carcinoma MDA-MB-435 cells in nude mice. It also reduced the metastatic potential of the MDA-MB-435 cells. Thus, endogenous TGFb appears to be necessary for the progression of these two carcinomas. Furthermore, when the tumor cells were mixed with Matrigel and embedded subcutaneously in nude mice, the blood volume in Matrigel plugs containing sRIII-expressing cells as indicated by hemoglobin levels was signi®cantly lower than that in Matrigel plugs containing the respective control cells. Blood vessel counts in para n sections of the Matrigel plugs containing sRIII-expressing cells were also signi®cantly lower than those in para n sections of the Matrigel plugs containing control cells. Treatment of human endothelial cells with a recombinant sRIII signi®cantly inhibited their ability to form a capillary web structure on Matrigel. These results for the ®rst time indicate that the sRIII-induced tumor suppression appears to be in part due to the inhibition of angiogenesis.

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“…Aberrant expression of HGF and c-met are found in various tumors of mesenchymal origin such as osteosarcomas, sarcomas of patients with Li ± Fraumeni syndrome, Kaposi sarcomas, melanomas and leukemias (Natali et al, 1993;Naidu et al, 1994;Rong et al, 1995;Ferracini et al, 1995). Similarly, overexpression of c-met and/or HGF was also found in dierent human carcinomas such as bladder, gastric, pancreatic, prostatic and thyroid carcinomas (Ebert et al, 1994;Humphrey et al, 1995;Di Renzo et al, 1995;Joseph et al, 1995). In breast carcinoma patients, overexpression of HGF correlates with poor prognosis (Yamashita et al, 1994).…”

Section: Introductionmentioning

confidence: 97%

Role of morphogenetic factors in metastasis of mammary carcinoma cells

et al. 1998

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We have analysed the role of the morphogenetic factors hepatocyte growth factor/scatter factor (HGF), neuregulin and E-cadherin in the process of metastasis and morphogenesis of mammary carcinoma cells. The cDNAs for HGF, neuregulin and E-cadherin were stably expressed in anaplastic human MDA MB 435 carcinoma cells. The altered cells were then injected into the mammary fat pads of nude mice, where they form tumors which can spontaneously metastasize to the lungs. We found that expression of HGF or neuregulin promoted metastasis whereas expression of the cell adhesion molecule E-cadherin was inhibitory. Moreover, expression of E-cadherin reconstituted the ability of the cells to form morphogenetic structures in matrigel cultures in response to HGF. These data demonstrate that HGF and neuregulin, which control branching or lobulo-alveolar morphogenesis of normal breast epithelium, do have metastasis-promoting eects on breast carcinoma cells. Moreover, our results suggest that the dierential activities of the two factors can be explained by the degree of epithelial dierentiation: induction of morphogenesis requires an intact epithelial adhesion and dierentiation system, whereas induction of metastasis is observed when the cells have lost their epithelial characteristics.

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Expression of Scatter Factor in Human Bladder Carcinoma

Abstract: Quantitation of SF in the urine and tumor deserves further study as a possible marker of urothelial malignancy.

Cited by 100 publications

References 0 publications

Hepatocyte Growth Factor/c-Met Signaling Promotes the Progression of Experimental Human Neuroblastomas

Hepatocyte Growth Factor/c-Met Signaling Promotes the Progression of Experimental Human Neuroblastomas

Extracellular domain of TGFβ type III receptor inhibits angiogenesis and tumor growth in human cancer cells

Role of morphogenetic factors in metastasis of mammary carcinoma cells

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