tailieunhanh - báo cáo hóa học:" Constitutive activation of BMP signalling abrogates experimental metastasis of OVCA429 cells via reduced cell adhesion"

Tuyển tập các báo cáo nghiên cứu về hóa học được đăng trên tạp chí sinh học quốc tế đề tài : Constitutive activation of BMP signalling abrogates experimental metastasis of OVCA429 cells via reduced cell adhesion | Shepherd et al. Journal of Ovarian Research 2010 3 5 http content 3 1 5 RESEARCH JOURNAL OF OVARIAN RESEARCH Open Access Constitutive activation of BMP signalling abrogates experimental metastasis of OVCA429 cells via reduced cell adhesion Trevor G Shepherd1 2 3 4 5 Michelle L Mujoomdar1 Mark W Nachtigal1 Abstract Background Activation of bone morphogenetic protein BMP 4 signalling in human ovarian cancer cells induces a number of phenotypic changes in vitro including altered cell morphology adhesion motility and invasion relative to normal human ovarian surface epithelial cells. From these in vitro analyses we had hypothesized that active BMP signalling promotes the metastatic potential of ovarian cancer. Methods To test this directly we engineered OVCA429 human ovarian cancer cells possessing doxycycline-inducible expression of a constitutively-active mutant BMP receptor ALK3QD and administered these cells to immunocompromised mice. Further characterization was performed in vitro to address the role of activated BMP signalling on the EOC phenotype with particular emphasis on epithelial-mesenchymal transition EMT and cell adhesion. Results Unexpectedly doxycycline-induced ALK3QD expression in OVCA429 cells reduced tumour implantation on peritoneal surfaces and ascites formation when xenografted into immunocompromised mice by intraperitoneal injection. To determine the potential mechanisms controlling this in vivo observation we followed with several cell culture experiments. Doxycycline-induced ALK3QD expression enhanced the refractile spindle-shaped morphology of cultured OVCA429 cells eliciting an EMT-like response. Using in vitro wound healing assays we observed that ALK3QD-expressing cells migrated with long cytoplasmic projections extending into the wound space. The phenotypic alterations of ALK3QD-expressing cells correlated with changes in specific gene expression patterns of EMT including increased Snail and Slug and reduced .

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