The expression of transforming growth factor-?1 is significantly correlated with the expression of vascular endothelial growth factor and poor prognosis of patients with advanced gastric carcinoma

Saito, Hiroaki; Tsujitani, Shunichi; Oka, Shinichi; Kondo, Akira; Ikeguchi, Masahide; Maeta, Michio; Kaibara, Nobuaki

doi:10.1002/(sici)1097-0142(19991015)86:8<1455::aid-cncr11>3.0.co;2-l

Cited by 135 publications

(86 citation statements)

References 35 publications

(16 reference statements)

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“…Though examples exist in which a cell's proliferative response to TGF-b switches from inhibition to stimulation in parallel with tumor progression (Hsu et al, 1994;Matsuzaki et al, 2000), attenuation of the autocrine loop by decreased expression of the TbRII receptor, leaving intact paracrine signaling to host cells is a frequently-implicated paradigm. Consistent with this formulation of the role of TGF-b in cancer, an association between increased production of TGF-b by tumors and worse clinical outcome has been noted for many epithelial cancers (Gorsch et al, 1992;Takanami et al, 1994;Friedman et al, 1995;Kinugasa et al, 1998;WikstroÈ m et al, 1998;Maehara et al, 1999;Saito et al, 1999). The experiments outlined in this study were designed to contrast in vivo and in vitro consequences of altered tumor cell TGF-b expression and responsiveness, and distinguish between autocrine and paracrine e ects.…”

Section: Discussionmentioning

confidence: 59%

Consequences of altered TGF-β expression and responsiveness in breast cancer: evidence for autocrine and paracrine effects

et al. 2002

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To characterize the impact of increased production of TGF-b in a xenograft model of human breast cancer, TGF-b-responsive MDA-231 cells were genetically modi®ed by stable transfection so as to increase their production of active TGF-b1. Compared with control cells, cells that produced increased amounts of TGF-b proliferated in vitro more slowly. In vivo, however, tumors derived from these cells exhibited increased proliferation and grew at an accelerated pace. To evaluate the role of autocrine TGF-b signaling, cells were also transfected with a dominant-negative truncated type II TGF-b receptor (TbRII). Disruption of autocrine TGF-b signaling in the TGF-b-overexpressing cells reduced their in vivo growth rate. Co-inoculation of Matrigel with the TGF-b-overexpressing cells expressing the truncated TbRII compensated for their diminished in vivo growth capacity, compared with the TGF-b-overexpressing cells with an intact autocrine loop. Tissue invasion by the tumor was a distinctive feature of the TGF-b-overexpressing cells, whether or not the autocrine loop was intact. Furthermore, tumors derived from TGFb-overexpressing cells, irrespective of the status of the autocrine TGF-b-signaling pathway, had a higher incidence of lung metastasis. Consistent with the suggestion that TGF-b's enhancement of invasion and metastasis is paracrine-based, we observed no signi®cant di erences among the cell clones in an in vitro invasion assay. Thus, in this experimental model system in vitro assays of cell proliferation and invasion do not accurately re¯ect in vivo observations, perhaps due to autocrine and paracrine e ects of TGF-b that in¯uence the important in vivo-based phenomena of tumor growth, invasion, and metastasis.

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Section: Discussionmentioning

confidence: 59%

Consequences of altered TGF-β expression and responsiveness in breast cancer: evidence for autocrine and paracrine effects

et al. 2002

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“…Consistent with this notion, increased TGFb1 expression by tumor cells correlated with tumor progression in non-small cell lung carcinoma (NSCLC), colorectal cancer, prostate cancer, and gastric carcinoma [13][14][15][16]. Additionally, intense TGFb staining has also been positively correlated with metastasis in breast carcinoma, prostate cancer, and colorectal cancer.…”

Section: Introductionmentioning

confidence: 62%

Roles of TGFβ in metastasis

2008

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The TGFβ signaling pathway is conserved from flies to humans and has been shown to regulate such diverse processes as cell proliferation, differentiation, motility, adhesion, organization, and programmed cell death. Both in vitro and in vivo experiments suggest that TGFβ can utilize these varied programs to promote cancer metastasis through its effects on the tumor microenvironment, enhanced invasive properties, and inhibition of immune cell function. Recent clinical evidence demonstrating a link between TGFβ signaling and cancer progression is fostering interest in this signaling pathway as a therapeutic target. Anti-TGFβ therapies are currently being developed and tested in preclinical studies. However, targeting TGFβ carries a substantial risk as this pathway is implicated in multiple homeostatic processes and is also known to have tumor-suppressor functions. Additionally, clinical and experimental results show that TGFβ has diverse and often conflicting roles in tumor progression even within the same tumor types. The development of TGFβ inhibitors for clinical use will require a deeper understanding of TGFβ signaling, its consequences, and the contexts in which it acts.

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“…In some circumstances, e.g., gastric sarcoma (Saito et al, 1999), it may stimulate angiogenesis by up-regulation of VEGF. TGF-␤ does not effect endothelial cell proliferation during intimal lesion formation (Smith et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Multiple growth factors regulate coronary embryonic vasculogenesis

Tomanek

Zheng

Peters

et al. 2001

Developmental Dynamics

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Mechanisms regulating coronary vascularization are not well understood. To test hypotheses regarding the influence of key growth factors and their interactions, we studied vascular tube formation (vasculogenesis) in collagen gels onto which quail embryonic ventricles were placed and incubated in the presence of growth factors or inhibitors. Vasculogenesis in this model is dependent on tyrosine kinase receptors, since tube formation was totally blocked by genestein. Tube formation was attenuated when anti-bFGF or anti-VEGF neutralizing antibodies were added to the medium and nearly completely inhibited when the both were added. The attenuation associated with anti-VEGF was due primarily to a decrease in assembly of endothelial cells, while that associated with bFGF was primarily due to a reduction in endothelial cells. Soluble tie-2, the receptor for angiopoietins, also had an inhibitory effect and, when added with either anti-bFGF or anti-VEGF, markedly attenuated tube formation. At optimal doses, tube formation was enhanced 6.5-fold by bFGF and 2.5-fold by VEGF over the controls. Each of these growth factors was dependent upon the other for optimal induction of tube formation, since neutralizing antibodies to one markedly reduced the potency of the other. VEGF potency was also markedly reduced when soluble tie-2 was added to the medium. Tube formation was virtually totally blocked by exogenous TGF-␤ at doses > 1 ng/ml, while neutralizing TGF-␤ antibodies enhanced tube formation 2-fold in the 30 ng-30 g range. These data provide the first documentation of multiple growth factor regulation of coronary tube formation.

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The expression of transforming growth factor-?1 is significantly correlated with the expression of vascular endothelial growth factor and poor prognosis of patients with advanced gastric carcinoma

Cited by 135 publications

References 35 publications

Consequences of altered TGF-β expression and responsiveness in breast cancer: evidence for autocrine and paracrine effects

Consequences of altered TGF-β expression and responsiveness in breast cancer: evidence for autocrine and paracrine effects

Roles of TGFβ in metastasis

Multiple growth factors regulate coronary embryonic vasculogenesis

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