Elevated plasma levels of transforming growth factor (TGF)-β1 and TGF-β2 in patients with disseminated malignant melanoma

Krasagakis, Konstantinos; Thölke, Daniela; Farthmann, B.; Eberle, Jürgen; Mansmann, Ulrich; Orfanos, C.E.

doi:10.1038/bjc.1998.245

Cited by 136 publications

(108 citation statements)

References 10 publications

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“…Circulating plasma levels of TGF-b1 and -b2, but not TGF-b3, can be exceedingly high in cancer patients, correlate with tumor grade, and decrease significantly following surgical tumor resection (Kong et al 1995;Krasagakis et al 1998;Shim et al 1999). In particular, TGF-b1 expression is frequently activated in response to many forms of cellular stress, such as during epithelial hyperplasia, where it serves a function in reestablishing homeostasis (Akhurst et al 1988;Cui et al 1995).…”

Section: Ligand Expression and Tgf-b Responsiveness In Human Tumorsmentioning

confidence: 99%

Targeting TGF-β Signaling for Therapeutic Gain

Akhurst

2017

Cold Spring Harb Perspect Biol

168

139

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Transforming growth factor bs (TGF-bs) are closely related ligands that have pleiotropic activity on most cell types of the body. They act through common heterotetrameric TGF-b type II and type I transmembrane dual specificity kinase receptor complexes, and the outcome of signaling is context-dependent. In normal tissue, they serve a role in maintaining homeostasis. In many diseased states, particularly fibrosis and cancer, TGF-b ligands are overexpressed and the outcome of signaling is diverted toward disease progression. There has therefore been a concerted effort to develop drugs that block TGF-b signaling for therapeutic benefit. This review will cover the basics of TGF-b signaling and its biological activities relevant to oncology, present a summary of pharmacological TGF-b blockade strategies, and give an update on preclinical and clinical trials for TGF-b blockade in a variety of solid tumor types.

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Section: Ligand Expression and Tgf-b Responsiveness In Human Tumorsmentioning

confidence: 99%

Targeting TGF-β Signaling for Therapeutic Gain

Akhurst

2017

Cold Spring Harb Perspect Biol

168

139

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“…The levels of TGF-β are higher in patients with disseminated melanoma when compared to those with localised disease (60). TGF-β has also been shown to induce the overproduction of IL-10 in tumors, leading to immunosuppression of antitumor responses.…”

Section: Activation Versus Suppression During Tumor Progressionmentioning

confidence: 99%

Escape from immunotherapy: possible mechanisms that influence tumor regression/progression

Ahmad

Rees

Ali

2004

Cancer Immunol Immunother

167

116

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“…In melanoma, high TGF-ß expression is correlated with a more aggressive phenotype and increased local infiltration, suggesting that TGF-ß may also stimulate the invasion of tumor cells to promote tumor progression (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Co-regulated expression of matrix metalloproteinase-2 and transforming growth factor-β in melanoma development and progression

Malaponte¹

2010

Oncol Rep

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Abstract. Previous studies have found that matrix metalloproteinase-2 (MMP-2) and transforming growth factor-ß (TGF-ß) can be considered as biomarkers and indices of disease progression in several human cancers. In this study, we investigated the plasma levels of MMP-2 and TGF-ß and their correlation in 49 primary cutaneous melanoma and 10 metastatic melanoma. Plasma MMP-2 and TGF-ß levels in patients with primary melanoma were significantly higher than those of healthy controls. These protein levels were significantly higher in patients with metastatic melanoma. A positive correlation between plasma levels of MMP-2 and TGF-ß in melanoma patients supports the hypothesis that TGF-ß triggers the release of MMP-2. The immunohistochemistry analysis shows that MMP-2 and TGF-ß were highly expressed in tumor tissues as well as in matched plasma samples. This finding suggests that these proteins are released from tumor cells. Overall, our data indicate that MMP-2 and TGF-ß may represent novel diagnostic markers and therapeutic targets in melanoma and the determination of their concentration could be a useful diagnostic and prognostic indicator. TGF-ß, leading the tissue invasion mediated by MMP-2, is a strong promoter of tumor progression. Therefore, reducing or blocking the activity of TGF-ß may represent a promising target in therapeutic strategies for limiting the growth of melanoma.

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Elevated plasma levels of transforming growth factor (TGF)-β1 and TGF-β2 in patients with disseminated malignant melanoma

Cited by 136 publications

References 10 publications

Targeting TGF-β Signaling for Therapeutic Gain

Targeting TGF-β Signaling for Therapeutic Gain

Escape from immunotherapy: possible mechanisms that influence tumor regression/progression

Co-regulated expression of matrix metalloproteinase-2 and transforming growth factor-β in melanoma development and progression

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