OBJECTIVE: Uterine leiomyoma produce an extracellular matrix (ECM) that is abnormal in its volume, content, and structure. Alterations in ECM can modify mechanical stress on cells and lead to activation of Rho-dependent signaling and cell growth. Here we sought to determine whether the altered ECM that is produced by leiomyoma was accompanied by an altered state of mechanical homeostasis. STUDY DESIGN: We measured the mechanical response of paired leiomyoma and myometrial samples and performed immunogold, confocal microscopy, and immunohistochemical analyses. RESULTS: Leiomyoma were significantly stiffer than matched myometrium. The increased stiffness was accompanied by alteration of the ECM, cell shape, and cytoskeleton in leiomyoma, compared with myometrial samples from the same uterus. Levels of AKAP13, a protein that is known to activate Rho, were increased in leiomyoma compared to myometrium. AKAP13 was associated with cytoskeletal filaments of immortalized leiomyoma cells. CONCLUSION: Leiomyoma cells are exposed to increased mechanical loading and show structural and biochemical features that are consistent with the activation of solid-state signaling.
OBJECTIVE: Uterine leiomyoma produce an extracellular matrix (ECM) that is abnormal in its volume, content, and structure. Alterations in ECM can modify mechanical stress on cells and lead to activation of Rho-dependent signaling and cell growth. Here we sought to determine whether the altered ECM that is produced by leiomyoma was accompanied by an altered state of mechanical homeostasis. STUDY DESIGN: We measured the mechanical response of paired leiomyoma and myometrial samples and performed immunogold, confocal microscopy, and immunohistochemical analyses. RESULTS:Leiomyoma were significantly stiffer than matched myometrium. The increased stiffness was accompanied by alteration of the ECM, cell shape, and cytoskeleton in leiomyoma, compared with myometrial samples from the same uterus. Levels of AKAP13, a protein that is known to activate Rho, were increased in leiomyoma compared to myometrium. AKAP13 was associated with cytoskeletal filaments of immortalized leiomyoma cells. CONCLUSION:Leiomyoma cells are exposed to increased mechanical loading and show structural and biochemical features that are consistent with the activation of solid-state signaling.
Authors: J C Tsibris; K B Porter; A Jazayeri; G Tzimas; H Nau; H Huang; K Kuparadze; G W Porter; W F O'Brien; W N Spellacy Journal: Cancer Res Date: 1999-11-15 Impact factor: 12.701
Authors: R L Mauck; M A Soltz; C C Wang; D D Wong; P H Chao; W B Valhmu; C T Hung; G A Ateshian Journal: J Biomech Eng Date: 2000-06 Impact factor: 2.097
Authors: Desireé M McCarthy-Keith; Minnie Malik; Joy Britten; James Segars; William H Catherino Journal: Fertil Steril Date: 2011-04-15 Impact factor: 7.329
Authors: Mark Payson; Minnie Malik; Sarah Siti-Nur Morris; James H Segars; Rebecca Chason; William H Catherino Journal: Fertil Steril Date: 2008-08-09 Impact factor: 7.329
Authors: Sagar Ghosh; Keith Ashcraft; Md Jamiul Jahid; Craig April; Cyrus M Ghajar; Jianhua Ruan; Howard Wang; Megan Foster; Daniel C Hughes; Amelie G Ramirez; Tim Huang; Jian-Bing Fan; Yanfen Hu; Rong Li Journal: Nat Commun Date: 2013 Impact factor: 14.919
Authors: James H Segars; Estella C Parrott; Joan D Nagel; Xiaoxiao Catherine Guo; Xiaohua Gao; Linda S Birnbaum; Vivian W Pinn; Darlene Dixon Journal: Hum Reprod Update Date: 2014-01-08 Impact factor: 15.610
Authors: Jeffrey T Thorne; Thalia R Segal; Sydney Chang; Soledad Jorge; James H Segars; Phyllis C Leppert Journal: Biol Reprod Date: 2014-11-19 Impact factor: 4.285
Authors: Tomoshige Kino; Hiroaki Takatori; Irini Manoli; Yonghong Wang; Anatoly Tiulpakov; Marc R Blackman; Yan A Su; George P Chrousos; Alan H DeCherney; James H Segars Journal: Sci Signal Date: 2009-02-10 Impact factor: 8.192