Autocrine stimulation of a human lung mesothelioma cell line is mediated through the transforming growth factor alpha/epidermal growth factor receptor mitogenic pathway

Mórocz, I; Schmitter, Doris; Lauber, Béatrice; Stahel, Rolf A.

doi:10.1038/bjc.1994.410

Cited by 34 publications

(13 citation statements)

References 34 publications

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“…EGFR expression has also been noted in MM cell lines. There is accumulating evidence that, despite being a favourable prognostic variable, EGFR forms part of an autocrine growth loop in MM cells [55].…”

Section: Discussionmentioning

confidence: 99%

EGFR expression: Associations with outcome and clinicopathological variables in malignant pleural mesothelioma

et al. 2006

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Section: Discussionmentioning

confidence: 99%

EGFR expression: Associations with outcome and clinicopathological variables in malignant pleural mesothelioma

et al. 2006

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“…It this regard, some authors report that this receptor is overexpressed more frequently or to higher levels in epithelioid than in non-epithelioid MMs [29,30]. EGFR and its cognate ligand transforming growth factor-alpha (TGF ) have been found to be co-expressed and to sustain an autocrine growth-stimulatory loop in MM cells [31]. In addition, the synthetic anilinoquinazoline EGFR inhibitor PD153035 was found to inhibit cell growth, VEGF production as well as motility and invasion in EGFR-overexpressing MM cells [32].…”

Section: Inhibition Of Growth Factor Receptor Signalingmentioning

confidence: 97%

Molecular Targets and Targeted Therapies for Malignant Mesothelioma

Palumbo

Bei

Procopio

et al. 2008

CMC

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Malignant mesothelioma is a highly invasive tumor originating from the mesothelial linings of the pleura, peritoneum and pericardium. It is seldom amenable to surgical intervention and poorly responsive to radiotherapy, leaving chemotherapy as the main therapeutic option for most patients. The development of effective drug regimens against mesothelioma has proven extremely difficult and a standard first-line treatment for patients with unresectable tumors has not been established until recently. Despite the benefits obtained with this newly validated standard of care, which is based on the combination of pemetrexed and cisplatin, the prognosis for mesothelioma patients remains poor, median survival is still less than two years and more active treatments are urgently needed. This article will focus on the molecular basis providing the rationale for targeted interventions against mesothelioma and will review targeted agents under evaluation as new potential therapeutic options for mesothelioma patients. Such agents include inhibitors of growth factor receptors, ligands and intracellular effectors. The agents targeting vascular endothelial growth factor signaling are of particular interest, due to the involvement of this pathway both in tumor angiogenesis and autocrine stimulation of mesothelioma cell growth. Alternative approaches are based on inhibitors of the ubiquitin-proteasome pathway and of histone deacetylases which, notwithstanding the functional divergence of the corresponding targets, share the ability to determine a wide modulation of the cancer cell phenotype that can lead to cell cycle arrest, apoptosis and sensitization to different antineoplastic treatments. A recombinant immunotoxin targeted to the membrane antigen mesothelin is an additional agent whose activity is being evaluated in mesothelioma patients.

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“…Despite the different responses of rat (41) and human mesothelial cells to exogenous EGF (29), there is evidence that TGF-a, a growth factor that binds to EGF-R, is an autocrine growth factor for rat (46) and human (27) (20,25), this is another potential modulator of the effects of WTI growth factor expression (35).…”

Section: Methodsmentioning

confidence: 99%

Growth Factor Responses and Protooncogene Expression of Murine Mesothelial Cell Lines Derived from Asbestos-Induced Mesotheliomas

et al. 1997

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Repeated intraperitoneal injections of crocidolite asbestos fibers induced diffuse malignant mesotheliomas in mice. A series of mesothelial cell lines was isolated from mice at different stages in the development of these tumors. The cell lines isolated from mice with mesotheliomas recapitulated their growth pattern in vivo and were tumorigenic when reinjected into syngeneic mice. Similar to human mesothelial cells, growth of the murine cell lines was stimulated by epidermal growth factor. Reactive mesothelial cells and mesotheliomas expressed the receptor for this growth factor. Crocidolite asbestos fibers have been reported to induce sustained expression of the c-fos and c-jun protooncogenes in rat pleural mesothelial cells in vitro (Heintz et al, Proc. Natl. Acad. Sci. USA 90: 3299-303, 1993). Human malignant mesotheliomas have been shown to express c-fos in situ (Ramael et al, Histol. Histopathol. 10: 639-643, 1995). Two of the cell lines derived from highly invasive murine mesotheliomas overexpressed c-fos and c-jun. This murine model recapitulates the histopathology, growth factor responses, and protooncogene expression of human malignant mesotheliomas.

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Autocrine stimulation of a human lung mesothelioma cell line is mediated through the transforming growth factor alpha/epidermal growth factor receptor mitogenic pathway

Cited by 34 publications

References 34 publications

EGFR expression: Associations with outcome and clinicopathological variables in malignant pleural mesothelioma

EGFR expression: Associations with outcome and clinicopathological variables in malignant pleural mesothelioma

Molecular Targets and Targeted Therapies for Malignant Mesothelioma

Growth Factor Responses and Protooncogene Expression of Murine Mesothelial Cell Lines Derived from Asbestos-Induced Mesotheliomas

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