Paclitaxel inhibits transforming growth factor-beta-increased urokinase-type plasminogen activator expression through p38 MAPK and RAW 264.7 macrophage migration
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2020
Authors
Mojsilović, Sonja
Tošić, Milica

Mojsilović, Slavko

Živanović, Marija
Bjelica, Sunčica

Srdić-Rajić, Tatjana

Santibanez, Juan

Article (Published version)

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Purpose: Transforming growth factor-beta (TGF-beta) induces alternative macrophage activation that favors tumor progression and immunosuppression. Meanwhile, paclitaxel (PTx) induces macrophage (M phi) polarization towards antitumor phenotype. TGF-beta also increases tumor stroma macrophage recruitment by mechanisms that include cell motility enhancement and extracellular matrix degradation. In this study, we aimed to determine whether PTx regulates macrophage migration and urokinase-type plasminogen activator (uPA) expression induced by TGF-beta. Methods: We used mouse macrophage RAW 264.7 cells treated with PTx and TGF-beta combinations. Proliferation was analyzed by MTT and cell cycle assays. Immunofluorescence was performed to determine tubulin cytoskeleton and Smad3 nuclear localization. Western blot and transcriptional luciferase reporters were used to measure signal transduction activation. Migration was determined by wound healing assay. uPA activity was determined by zymograph...y assay. Results: PTx decreased RAW 264.7 cell proliferation by inducing G2/M cell cycle arrest and profoundly modified the tubulin cytoskeleton. Also, PTx inhibited TGF-beta-induced Smad3 activation. Furthermore, PTx decreased cell migration and uPA expression stimulated by TGF-beta. Remarkably, p38 MAPK mediated PTx inhibition of uPA activity induced by TGF-beta but it was not implicated on cell migration inhibition. Conclusions: PTx inhibits TGF-beta induction of mouse M phi migration and uPA expression, suggesting that PTx, as TGF-beta targeting therapy, may enhance MT anticancer action within tumors.
Keywords:
macrophages / migration / paclitaxel / proliferation / transforming growth factor-beta / urokinase-type plasminogen activatorSource:
Journal of BUON, 2020, 25, 2, 1257-1265Publisher:
- Balkan Union of Oncology (B.U.ON.)
Funding / projects:
- The pathogenetic mechanism in hematological malignancies (RS-175053)
- Pharmacodynamic and pharmacogenomic research of new drugs in the treatment of solid tumors (RS-41026)
- Regenerative and modulatory potential of adult stem cells (RS-175062)
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Institut za medicinska istraživanjaTY - JOUR AU - Mojsilović, Sonja AU - Tošić, Milica AU - Mojsilović, Slavko AU - Živanović, Marija AU - Bjelica, Sunčica AU - Srdić-Rajić, Tatjana AU - Santibanez, Juan PY - 2020 UR - http://rimi.imi.bg.ac.rs/handle/123456789/1067 AB - Purpose: Transforming growth factor-beta (TGF-beta) induces alternative macrophage activation that favors tumor progression and immunosuppression. Meanwhile, paclitaxel (PTx) induces macrophage (M phi) polarization towards antitumor phenotype. TGF-beta also increases tumor stroma macrophage recruitment by mechanisms that include cell motility enhancement and extracellular matrix degradation. In this study, we aimed to determine whether PTx regulates macrophage migration and urokinase-type plasminogen activator (uPA) expression induced by TGF-beta. Methods: We used mouse macrophage RAW 264.7 cells treated with PTx and TGF-beta combinations. Proliferation was analyzed by MTT and cell cycle assays. Immunofluorescence was performed to determine tubulin cytoskeleton and Smad3 nuclear localization. Western blot and transcriptional luciferase reporters were used to measure signal transduction activation. Migration was determined by wound healing assay. uPA activity was determined by zymography assay. Results: PTx decreased RAW 264.7 cell proliferation by inducing G2/M cell cycle arrest and profoundly modified the tubulin cytoskeleton. Also, PTx inhibited TGF-beta-induced Smad3 activation. Furthermore, PTx decreased cell migration and uPA expression stimulated by TGF-beta. Remarkably, p38 MAPK mediated PTx inhibition of uPA activity induced by TGF-beta but it was not implicated on cell migration inhibition. Conclusions: PTx inhibits TGF-beta induction of mouse M phi migration and uPA expression, suggesting that PTx, as TGF-beta targeting therapy, may enhance MT anticancer action within tumors. PB - Balkan Union of Oncology (B.U.ON.) T2 - Journal of BUON T1 - Paclitaxel inhibits transforming growth factor-beta-increased urokinase-type plasminogen activator expression through p38 MAPK and RAW 264.7 macrophage migration EP - 1265 IS - 2 SP - 1257 VL - 25 UR - https://hdl.handle.net/21.15107/rcub_rimi_1067 ER -
@article{ author = "Mojsilović, Sonja and Tošić, Milica and Mojsilović, Slavko and Živanović, Marija and Bjelica, Sunčica and Srdić-Rajić, Tatjana and Santibanez, Juan", year = "2020", abstract = "Purpose: Transforming growth factor-beta (TGF-beta) induces alternative macrophage activation that favors tumor progression and immunosuppression. Meanwhile, paclitaxel (PTx) induces macrophage (M phi) polarization towards antitumor phenotype. TGF-beta also increases tumor stroma macrophage recruitment by mechanisms that include cell motility enhancement and extracellular matrix degradation. In this study, we aimed to determine whether PTx regulates macrophage migration and urokinase-type plasminogen activator (uPA) expression induced by TGF-beta. Methods: We used mouse macrophage RAW 264.7 cells treated with PTx and TGF-beta combinations. Proliferation was analyzed by MTT and cell cycle assays. Immunofluorescence was performed to determine tubulin cytoskeleton and Smad3 nuclear localization. Western blot and transcriptional luciferase reporters were used to measure signal transduction activation. Migration was determined by wound healing assay. uPA activity was determined by zymography assay. Results: PTx decreased RAW 264.7 cell proliferation by inducing G2/M cell cycle arrest and profoundly modified the tubulin cytoskeleton. Also, PTx inhibited TGF-beta-induced Smad3 activation. Furthermore, PTx decreased cell migration and uPA expression stimulated by TGF-beta. Remarkably, p38 MAPK mediated PTx inhibition of uPA activity induced by TGF-beta but it was not implicated on cell migration inhibition. Conclusions: PTx inhibits TGF-beta induction of mouse M phi migration and uPA expression, suggesting that PTx, as TGF-beta targeting therapy, may enhance MT anticancer action within tumors.", publisher = "Balkan Union of Oncology (B.U.ON.)", journal = "Journal of BUON", title = "Paclitaxel inhibits transforming growth factor-beta-increased urokinase-type plasminogen activator expression through p38 MAPK and RAW 264.7 macrophage migration", pages = "1265-1257", number = "2", volume = "25", url = "https://hdl.handle.net/21.15107/rcub_rimi_1067" }
Mojsilović, S., Tošić, M., Mojsilović, S., Živanović, M., Bjelica, S., Srdić-Rajić, T.,& Santibanez, J.. (2020). Paclitaxel inhibits transforming growth factor-beta-increased urokinase-type plasminogen activator expression through p38 MAPK and RAW 264.7 macrophage migration. in Journal of BUON Balkan Union of Oncology (B.U.ON.)., 25(2), 1257-1265. https://hdl.handle.net/21.15107/rcub_rimi_1067
Mojsilović S, Tošić M, Mojsilović S, Živanović M, Bjelica S, Srdić-Rajić T, Santibanez J. Paclitaxel inhibits transforming growth factor-beta-increased urokinase-type plasminogen activator expression through p38 MAPK and RAW 264.7 macrophage migration. in Journal of BUON. 2020;25(2):1257-1265. https://hdl.handle.net/21.15107/rcub_rimi_1067 .
Mojsilović, Sonja, Tošić, Milica, Mojsilović, Slavko, Živanović, Marija, Bjelica, Sunčica, Srdić-Rajić, Tatjana, Santibanez, Juan, "Paclitaxel inhibits transforming growth factor-beta-increased urokinase-type plasminogen activator expression through p38 MAPK and RAW 264.7 macrophage migration" in Journal of BUON, 25, no. 2 (2020):1257-1265, https://hdl.handle.net/21.15107/rcub_rimi_1067 .