BACKGROUND: Although inflammatory breast cancer (IBC) is recognized as the most lethal variant of locally advanced breast cancer, few molecular signatures of IBC have been identified that can be used as targets to develop therapeutics that effectively inhibit the aggressive phenotype displayed by IBC tumors. METHODS: Real-time polymerase chain reaction analysis, Western blot analysis, modified Boyden chamber invasion assays, vasculogenic mimicry (VM) assays, and gelatin zymography were used in the current studies. Agonists and antagonists of the prostanoid receptors EP3 and EP4 and of EP4 short-hairpin RNA (shRNA) knockdown approaches were used as tools to assess the role of prostanoid receptors EP3 and EP4 in the regulation of specific biologic activities of IBC cells. RESULTS: The current studies revealed that the IBC breast cancer cell lines SUM149 and SUM190 express high levels of cyclooxygenase-2 messenger RNA and protein, produce abundant levels of prostaglandin E(2), and produce both EP3 and EP4 receptor proteins. Studies using the EP4 antagonist GW627368X and shRNA molecular knockdown approaches revealed a role for EP4 in regulating invasion of IBC cells. EP3, but not EP4, regulated the ability of SUM149 cells to undergo VM, which is the ability to form capillary-like structures, a characteristic exhibited by very aggressive tumor types. Inhibition of VM by sulprostone was associated with an inhibition of matrix metalloprotease-2 (MMP-2) enzyme activity. CONCLUSIONS: The prostanoid receptors EP3 and EP4 differentially regulate activities exhibited by IBC cells that have been associated with the aggressive phenotype of this lethal variant of breast cancer. Whereas EP4 regulates invasion, EP3 regulates VM and the associated increased MMP-2 enzyme activity. Copyright 2010 American Cancer Society.
BACKGROUND: Although inflammatory breast cancer (IBC) is recognized as the most lethal variant of locally advanced breast cancer, few molecular signatures of IBC have been identified that can be used as targets to develop therapeutics that effectively inhibit the aggressive phenotype displayed by IBC tumors. METHODS: Real-time polymerase chain reaction analysis, Western blot analysis, modified Boyden chamber invasion assays, vasculogenic mimicry (VM) assays, and gelatin zymography were used in the current studies. Agonists and antagonists of the prostanoid receptors EP3 and EP4 and of EP4 short-hairpin RNA (shRNA) knockdown approaches were used as tools to assess the role of prostanoid receptors EP3 and EP4 in the regulation of specific biologic activities of IBC cells. RESULTS: The current studies revealed that the IBC breast cancer cell lines SUM149 and SUM190 express high levels of cyclooxygenase-2 messenger RNA and protein, produce abundant levels of prostaglandin E(2), and produce both EP3 and EP4 receptor proteins. Studies using the EP4 antagonist GW627368X and shRNA molecular knockdown approaches revealed a role for EP4 in regulating invasion of IBC cells. EP3, but not EP4, regulated the ability of SUM149 cells to undergo VM, which is the ability to form capillary-like structures, a characteristic exhibited by very aggressive tumor types. Inhibition of VM by sulprostone was associated with an inhibition of matrix metalloprotease-2 (MMP-2) enzyme activity. CONCLUSIONS: The prostanoid receptors EP3 and EP4 differentially regulate activities exhibited by IBC cells that have been associated with the aggressive phenotype of this lethal variant of breast cancer. Whereas EP4 regulates invasion, EP3 regulates VM and the associated increased MMP-2 enzyme activity. Copyright 2010 American Cancer Society.
Authors: N T Ueno; A U Buzdar; S E Singletary; F C Ames; M D McNeese; F A Holmes; R L Theriault; E A Strom; B J Wasaff; L Asmar; D Frye; G N Hortobagyi Journal: Cancer Chemother Pharmacol Date: 1997 Impact factor: 3.333
Authors: Li Yang; Yuhui Huang; Rut Porta; Kiyoshi Yanagisawa; Adriana Gonzalez; Eric Segi; David H Johnson; Shuh Narumiya; David P Carbone Journal: Cancer Res Date: 2006-10-01 Impact factor: 12.701
Authors: Richard J Wilson; Gerard M P Giblin; Susan Roomans; Sharron A Rhodes; Kerri-Ann Cartwright; Vanessa J Shield; Jason Brown; Alan Wise; Jannatara Chowdhury; Sara Pritchard; Jim Coote; Lloyd S Noel; Terry Kenakin; Cynthia L Burns-Kurtis; Valerie Morrison; David W Gray; Heather Giles Journal: Br J Pharmacol Date: 2006-06 Impact factor: 8.739
Authors: Ilse Van der Auwera; Steven J Van Laere; Gert G Van den Eynden; Ina Benoy; Peter van Dam; Cecile G Colpaert; Stephen B Fox; Helen Turley; Adrian L Harris; Eric A Van Marck; Peter B Vermeulen; Luc Y Dirix Journal: Clin Cancer Res Date: 2004-12-01 Impact factor: 12.531
Authors: Gargi D Basu; Latha B Pathangey; Teresa L Tinder; Sandra J Gendler; Pinku Mukherjee Journal: Breast Cancer Res Date: 2005-04-04 Impact factor: 6.466
Authors: Stephen P Ethier; Stephen T Guest; Elizabeth Garrett-Mayer; Kent Armeson; Robert C Wilson; Kathryn Duchinski; Daniel Couch; Joe W Gray; Christiana Kappler Journal: NPJ Breast Cancer Date: 2020-07-21
Authors: Dawn A Kirschmann; Elisabeth A Seftor; Katharine M Hardy; Richard E B Seftor; Mary J C Hendrix Journal: Clin Cancer Res Date: 2012-04-02 Impact factor: 12.531
Authors: Todd L Edwards; Martha J Shrubsole; Qiuyin Cai; Guoliang Li; Qi Dai; Douglas K Rex; Thomas M Ulbright; Zhenming Fu; Harvey J Murff; Walter Smalley; Reid Ness; Wei Zheng Journal: Cancer Prev Res (Phila) Date: 2012-05-02
Authors: Mary J C Hendrix; Elisabeth A Seftor; Richard E B Seftor; Jun-Tzu Chao; Du-Shieng Chien; Yi-Wen Chu Journal: Pharmacol Ther Date: 2016-01-22 Impact factor: 12.310
Authors: Richard E B Seftor; Angela R Hess; Elisabeth A Seftor; Dawn A Kirschmann; Katharine M Hardy; Naira V Margaryan; Mary J C Hendrix Journal: Am J Pathol Date: 2012-08-31 Impact factor: 4.307