Receptor of Activated Protein C Promotes Metastasis and Correlates with Clinical Outcome in Lung Adenocarcinoma

• DOI: 10.1164/rccm.201110-1826oc
• Publication Date: 2012-03-30T06:03:51Z
• Authors: Iker Antón; Eva Molina; Diego Luis-Ravelo; Carolina Zandueta; Karmele Valencia; Cristina Ormazabal; Susana Martínez-C...; Naiara Perurena; María José Pajares; Jackeline Agorreta; Luis M. Montuenga; Victor Segura; Ignacio I. Wistuba; Javier De Las Rivas; José Hermida; Fernando Lecanda
• Keywords: Tissue microarray

Efficient metastasis requires survival and adaptation of tumor cells to stringent conditions imposed by the extracellular milieu. Identification critical signaling pathways in might unveil novel targets relevant disease progression.To investigate contribution activated protein C (APC) its receptor (endothelial [EPCR]) animal models lung cancer patients with adenocarcinoma.Signaling pathway triggered APC/EPCR relevance apoptosis was studied vitro. Functional significance assessed silencing blocking antibodies several vivo athymic nude Foxn1(nu) mice. We examined EPCR levels using a microarray dataset 107 patients. Immunohistochemical analysis performed an independent cohort 295 adenocarcinoma.The effects APC binding rapidly Akt signal-regulated kinase pathways, leading attenuated vitro apoptosis. In vivo, expression or interaction reduced infiltration target organ, resulting impaired prometastatic activity. Moreover, overexpression induced increased metastatic activity organs. Analysis clinical samples showed robust association between high poor prognosis, particularly stage I patients.EPCR ligand promote cell that contributes endurance stress favoring adenocarcinoma. EPCR/APC is outcome early-stage cancer.