Evidence for a positive role of transforming growth factor-β in human breast cancer cell tumorigenesis

Arteaga, Carlos L.; Dugger, Teresa C.; Winnier, Angela R.; Forbes, James T.

doi:10.1002/jcb.240531134

Cited by 26 publications

(9 citation statements)

References 17 publications

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“…The earliest report of this activity with an anti-ErbB2 MAb (Hancock et al, 1991) has been followed by many laboratory studies showing that anti-ErbB2 MAbs can markedly enhance or promote sensitivity to the antitumor e ects of the chemotherapeutic agent cisplatin and other drugs (Arteaga et al, 1993(Arteaga et al, , 1994Pietras et al, 1994Pietras et al, , 1998Pegram et al, 1997bPegram et al, , 1999.…”

Section: Preclinical Studies With Anti-erbb2 Monoclonal Antibodiesmentioning

confidence: 99%

The EGF receptor family as targets for cancer therapy

2000

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Human carcinomas frequently express high levels of receptors in the EGF receptor family, and overexpression of at least two of these receptors, the EGF receptor (EGFr) and closely related ErbB2, has been associated with a more aggressive clinical behavior. Further, transfection or activation of high levels of these two receptors in nonmalignant cell lines can lead to a transformed phenotype. For these reasons therapies directed at preventing the function of these receptors have the potential to be useful anti-cancer treatments. In the last two decades monoclonal antibodies (MAbs) which block activation of the EGFr and ErbB2 have been developed. These MAbs have shown promising preclinical activity and`chimeric' and`humanized' MAbs have been produced in order to obviate the problem of host immune reactions. Clinical activity with these antibodies has been documented: trastuzumab, a humanized anti-ErbB2 MAb, is active and was recently approved in combination with paclitaxel for the therapy of patients with metastatic ErbB2-overexpressing breast cancer; IMC-C225, a chimeric anti-EGFr MAb, has shown impressive activity when combined with radiation therapy and reverses resistance to chemotherapy. In addition to antibodies, compounds that directly inhibit receptor tyrosine kinases have shown preclinical activity and early clinical activity has been reported. A series of phase III studies with these antibodies and direct tyrosine kinase inhibitors are ongoing or planned, and will further address the role of these active anti-receptor agents in the treatment of patients with cancer. Oncogene (2000) 19, 6550 ± 6565.

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Section: Preclinical Studies With Anti-erbb2 Monoclonal Antibodiesmentioning

confidence: 99%

The EGF receptor family as targets for cancer therapy

2000

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“…and separate groups were treated with a neutralizing anti-TGF-␤ Ab, control Ig, or nothing as described in Materials and Methods. The neutralizing mAb is against the TGF-␤ PAN region, which effectively blocks both TGF-␤1 and -␤2 (27). All mice were sacrificed on wk 8 p.i.…”

Section: Tgf-␤1 Blockade Fails To Regulate the Development Of Il-13-dmentioning

confidence: 99%

IL-13 Activates a Mechanism of Tissue Fibrosis That Is Completely TGF-β Independent

Kaviratne

Hesse

Leusink

et al. 2004

The Journal of Immunology

335

244

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Fibrosis is a characteristic feature in the pathogenesis of a wide spectrum of diseases. Recently, it was suggested that IL-13-dependent fibrosis develops through a TGF-β1 and matrix metalloproteinase-9-dependent (MMP-9) mechanism. However, the significance of this pathway in a natural disorder of fibrosis was not investigated. In this study, we examined the role of TGF-β in IL-13-dependent liver fibrosis caused by Schistosoma mansoni infection. Infected IL-13−/− mice showed an almost complete abrogation of fibrosis despite continued and undiminished production of TGF-β1. Although MMP-9 activity was implicated in the IL-13 pathway, MMP-9−/− mice displayed no reduction in fibrosis, even when chronically infected. To directly test the requirement for TGF-β, studies were also performed with neutralizing anti-TGF-β Abs, soluble antagonists (soluble TGF-βR-Fc), and Tg mice (Smad3−/− and TGF-βRII-Fc Tg) that have disruptions in all or part of the TGF-β signaling cascade. In all cases, fibrosis developed normally and with kinetics similar to wild-type mice. Production of IL-13 was also unaffected. Finally, several genes, including interstitial collagens, several MMPs, and tissue inhibitors of metalloprotease-1 were up-regulated in TGF-β1−/− mice by IL-13, demonstrating that IL-13 activates the fibrogenic machinery directly. Together, these studies provide unequivocal evidence of a pathway of fibrogenesis that is IL-13 dependent but TGF-β1 independent, illustrating the importance of targeting IL-13 directly in the treatment of infection-induced fibrosis.

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“…Furthermore, this lack of useful tumor markers makes it difficult to identify patients with resectable nonsmall cell lung carcinoma who might benefit from adjuvant therapy. The prototype of the multifunctional growth factor, transforming growth factor-␤1 (TGF␤1), is overexpressed locally in many tumors, and is believed to play a role in tumor transformation, 3,4 progression, 5 and regression. 4,6,7 In addition, the plasma TGF␤1 level has been found to be increased at the time of diagnosis in patients with a variety of tumors including hepatocellular carcinoma, 8,9 prostate carcinoma, 10,11 cervical carcinoma, 12,13 Hodgkin disease, 12,13 breast carcinoma, 13,14 and both small cell and nonsmall cell lung carcinoma.…”

mentioning

confidence: 99%