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.
TY - 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 .
