BACKGROUND: Cell adhesion plays an important role in proliferation, metastasis, and tumor growth and may represent a potential vulnerability in treatment of prostate cancer patients. Bicalutamide (Casodex) has been used as an anti-androgen agent for prostate cancer patients during hormone ablation therapy. This study focuses on the effect of Bicalutamide on cell adhesion to fibronectin (FN) in prostate cancer cells. METHODS: Androgen-dependent LNCaP prostate cancer cells were stimulated with androgen before being irradiated with doses of 0, 5, 10, or 15 Gy. Cell adhesion to fibronectin was then measured to ascertain androgen's role in integrin mediated prostate cancer cell adhesion. Flow cytometry was used to analyze surface expression of integrin subtypes in LNCaP cells. RESULTS: LNCaP cell adhesion to FN was significantly increased by stimulation with androgen when treated with 10 or 15 Gy ionizing radiations but not at 0 or 5 Gy. This increase was inhibited by treatment with Bicalutamide. LNCaP cells exposed to high dose radiation showed an increased expression of alpha(V) and beta(1) integrins in response to androgen treatment while Bicalutamide abolished this effect. CONCLUSIONS: Our data show that Bicalutamide inhibits the effect of androgen on cell adhesion to FN through changes of integrin subtypes in cells given high dose radiation. This suggests new molecular targets and possible treatment strategies for prostate cancer patients to improve the outcome during hormone ablation therapy and radiation therapy.
BACKGROUND: Cell adhesion plays an important role in proliferation, metastasis, and tumor growth and may represent a potential vulnerability in treatment of prostate cancerpatients. Bicalutamide (Casodex) has been used as an anti-androgen agent for prostate cancerpatients during hormone ablation therapy. This study focuses on the effect of Bicalutamide on cell adhesion to fibronectin (FN) in prostate cancer cells. METHODS: Androgen-dependent LNCaP prostate cancer cells were stimulated with androgen before being irradiated with doses of 0, 5, 10, or 15 Gy. Cell adhesion to fibronectin was then measured to ascertain androgen's role in integrin mediated prostate cancer cell adhesion. Flow cytometry was used to analyze surface expression of integrin subtypes in LNCaP cells. RESULTS:LNCaP cell adhesion to FN was significantly increased by stimulation with androgen when treated with 10 or 15 Gy ionizing radiations but not at 0 or 5 Gy. This increase was inhibited by treatment with Bicalutamide. LNCaP cells exposed to high dose radiation showed an increased expression of alpha(V) and beta(1) integrins in response to androgen treatment while Bicalutamide abolished this effect. CONCLUSIONS: Our data show that Bicalutamide inhibits the effect of androgen on cell adhesion to FN through changes of integrin subtypes in cells given high dose radiation. This suggests new molecular targets and possible treatment strategies for prostate cancerpatients to improve the outcome during hormone ablation therapy and radiation therapy.
Authors: Amir Abdollahi; Kenneth E Lipson; Xiaohong Han; Robert Krempien; Thuy Trinh; Klaus J Weber; Philip Hahnfeldt; Lynn Hlatky; Juergen Debus; Anthony R Howlett; Peter E Huber Journal: Cancer Res Date: 2003-07-01 Impact factor: 12.701
Authors: Colleen A Lawton; Michelle DeSilvio; Mack Roach; Valery Uhl; Robert Kirsch; Michael Seider; Marvin Rotman; Christopher Jones; Sucha Asbell; Richard Valicenti; Stephen Hahn; Charles R Thomas Journal: Int J Radiat Oncol Biol Phys Date: 2007-05-24 Impact factor: 7.038
Authors: Sangita C Pawar; Shona Dougherty; Michael E Pennington; Manolis C Demetriou; B Dino Stea; Robert T Dorr; Anne E Cress Journal: Int J Radiat Biol Date: 2007 Nov-Dec Impact factor: 2.694
Authors: Tao Wang; Jiayi Huang; Mai Vue; Michael R Alavian; Hira Lal Goel; Dario C Altieri; Lucia R Languino; Thomas J FitzGerald Journal: Mol Cancer Res Date: 2018-09-28 Impact factor: 5.852
Authors: Tao Wang; Lucia R Languino; Jane Lian; Gary Stein; Michael Blute; Thomas J Fitzgerald Journal: Front Oncol Date: 2011-07-13 Impact factor: 6.244
Authors: Mark Sutherland; Andrew Gordon; Steven D Shnyder; Laurence H Patterson; Helen M Sheldrake Journal: Cancers (Basel) Date: 2012-10-26 Impact factor: 6.639