ABS ePoster Library

In vitro evidence for the role of procoagulant stromal fibroblasts in the development of breast cancer
Association of Breast Surgery ePoster Library. Kirwan C. 05/15/17; 166199; P016
Ms. Cliona Kirwan
Ms. Cliona Kirwan
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Abstract
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Introduction: Tumour stroma resembles a non-healing wound, where a procoagulant environment creates a permissive milieu for cancer growth. However we have previously shown that stromal fibroblasts develop a procoagulant phenotype at the preinvasive stage. We aimed to determine whether procoagulant fibroblasts are functional in tumour development. Methods: MCF10a ('normal') and DCIS.com cells were i)cultured in control (cont) vs TF-conditioned media(TF-CM, from TF-overexpressing fibroblasts[TFOFs] and ii)co-cultured with control fibroblasts and TFOFs, +/- Rivaroxaban (TF-cofactor inhibitor) or Dabigatran (thrombin inhibitor). Acini size was determined. Results: In all experiments, acini formation increased in the presence of TF-conditioned media and TFOF co-culture, compared to control, with this effect abrogated by Rivaroxaban(R) and Dabigatran(D).
Conclusions: The acini-promoting effects of procoagulant fibroblasts is abrogated by anticoagulants. Coagulation represents a novel therapeutic target in breast cancer development.
Introduction: Tumour stroma resembles a non-healing wound, where a procoagulant environment creates a permissive milieu for cancer growth. However we have previously shown that stromal fibroblasts develop a procoagulant phenotype at the preinvasive stage. We aimed to determine whether procoagulant fibroblasts are functional in tumour development. Methods: MCF10a ('normal') and DCIS.com cells were i)cultured in control (cont) vs TF-conditioned media(TF-CM, from TF-overexpressing fibroblasts[TFOFs] and ii)co-cultured with control fibroblasts and TFOFs, +/- Rivaroxaban (TF-cofactor inhibitor) or Dabigatran (thrombin inhibitor). Acini size was determined. Results: In all experiments, acini formation increased in the presence of TF-conditioned media and TFOF co-culture, compared to control, with this effect abrogated by Rivaroxaban(R) and Dabigatran(D).
Conclusions: The acini-promoting effects of procoagulant fibroblasts is abrogated by anticoagulants. Coagulation represents a novel therapeutic target in breast cancer development.
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