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Article: Endogenous expression of transforming growth factor β1 inhibits growth and tumorigenicity and enhances fas-mediated apoptosis in a murine high- grade glioma model
Title | Endogenous expression of transforming growth factor β1 inhibits growth and tumorigenicity and enhances fas-mediated apoptosis in a murine high- grade glioma model |
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Authors | |
Issue Date | 1998 |
Citation | Cancer Research, 1998, v. 58, n. 2, p. 302-309 How to Cite? |
Abstract | It has been hypothesized that transforming growth factor β (TGF-β) may prevent immune-mediated glioma cell elimination; however, previous work has also indicated that increased TGF-β may lead to reduced proliferation, induction of apoptosis, and enhancement of Fas-induced apoptosis. We have investigated the role of TGF-β in the progression of malignant glioma using an immunocompetent murine model. SMA 560 malignant glioma cells were stably transfected with constructs that resulted in over- or underproduction of active TGF-β1. Using these cell lines, we have shown that (a) TGF-β1 inhibits induction of antitumor cytotoxicity when the tumor cells are given s.c. but not when they are given intracranially; (b) Fas/APO-1 is expressed on SMA 560 cells in vitro and in vivo, SMA 560 cells are susceptible to TGF- β1- and Fas-induced apoptosis in vitro, and TGF-β1 and Fas act synergistically to induce glioma cell death; (c) increased levels of endogenous TGF-β1 production by SMA 560 cells lead to increased sensitivity to Fas-mediated apoptosis; (d) overproduction of endogenous TGF-β1 reduces the rate of s.c. SMA 560 tumor growth and also reduces the tumorigenicity of tumors located in the central nervous system, with opposite effects observed with under-production of TGF-β1 using antisense cell lines; and (e) the observed changes in growth parameters in vivo were associated with increased rates of apoptosis in TGF-β1-overproducing cells. Taken together, these results indicate that, despite decreased induction of CTL responses, the dominant net effect of TGF-β1 on the growth of the SMA 560 murine high- grade glioma in vivo is growth inhibition. This contrasts with results seen with non-central nervous system malignant tumors in immunocompetent animals, in which TGF-β1 production provides a major growth advantage. |
Persistent Identifier | http://hdl.handle.net/10722/266764 |
ISSN | 2023 Impact Factor: 12.5 2023 SCImago Journal Rankings: 3.468 |
DC Field | Value | Language |
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dc.contributor.author | Ashley, David M. | - |
dc.contributor.author | Kong, Feng M. | - |
dc.contributor.author | Bigner, Darell D. | - |
dc.contributor.author | Hale, Laura P. | - |
dc.date.accessioned | 2019-01-31T07:19:31Z | - |
dc.date.available | 2019-01-31T07:19:31Z | - |
dc.date.issued | 1998 | - |
dc.identifier.citation | Cancer Research, 1998, v. 58, n. 2, p. 302-309 | - |
dc.identifier.issn | 0008-5472 | - |
dc.identifier.uri | http://hdl.handle.net/10722/266764 | - |
dc.description.abstract | It has been hypothesized that transforming growth factor β (TGF-β) may prevent immune-mediated glioma cell elimination; however, previous work has also indicated that increased TGF-β may lead to reduced proliferation, induction of apoptosis, and enhancement of Fas-induced apoptosis. We have investigated the role of TGF-β in the progression of malignant glioma using an immunocompetent murine model. SMA 560 malignant glioma cells were stably transfected with constructs that resulted in over- or underproduction of active TGF-β1. Using these cell lines, we have shown that (a) TGF-β1 inhibits induction of antitumor cytotoxicity when the tumor cells are given s.c. but not when they are given intracranially; (b) Fas/APO-1 is expressed on SMA 560 cells in vitro and in vivo, SMA 560 cells are susceptible to TGF- β1- and Fas-induced apoptosis in vitro, and TGF-β1 and Fas act synergistically to induce glioma cell death; (c) increased levels of endogenous TGF-β1 production by SMA 560 cells lead to increased sensitivity to Fas-mediated apoptosis; (d) overproduction of endogenous TGF-β1 reduces the rate of s.c. SMA 560 tumor growth and also reduces the tumorigenicity of tumors located in the central nervous system, with opposite effects observed with under-production of TGF-β1 using antisense cell lines; and (e) the observed changes in growth parameters in vivo were associated with increased rates of apoptosis in TGF-β1-overproducing cells. Taken together, these results indicate that, despite decreased induction of CTL responses, the dominant net effect of TGF-β1 on the growth of the SMA 560 murine high- grade glioma in vivo is growth inhibition. This contrasts with results seen with non-central nervous system malignant tumors in immunocompetent animals, in which TGF-β1 production provides a major growth advantage. | - |
dc.language | eng | - |
dc.relation.ispartof | Cancer Research | - |
dc.title | Endogenous expression of transforming growth factor β1 inhibits growth and tumorigenicity and enhances fas-mediated apoptosis in a murine high- grade glioma model | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.pmid | 9443409 | - |
dc.identifier.scopus | eid_2-s2.0-0031964370 | - |
dc.identifier.volume | 58 | - |
dc.identifier.issue | 2 | - |
dc.identifier.spage | 302 | - |
dc.identifier.epage | 309 | - |
dc.identifier.issnl | 0008-5472 | - |