Unveiling the role of osteosarcoma-derived secretome in premetastatic lung remodelling.
Sara F F AlmeidaLiliana SantosGabriela Sampaio-RibeiroHugo R S FerreiraNuno LimaRui CaetanoMónica AbreuMónica ZuzarteAna Sofia RibeiroArtur PaivaTânia Martins-MarquesPaulo TeixeiraRui AlmeidaJosé Manuel CasanovaHenrique GirãoAntero J AbrunhosaCélia M F GomesPublished in: Journal of experimental & clinical cancer research : CR (2023)
Integration of our data uncovers neutrophil infiltration and the functional contribution of stromal-activated fibroblasts in ECM remodelling for tumour cell attachment as early pro-metastatic events, which may hold therapeutic potential in preventing or slowing the metastatic spread. Moreover, we identified EFEMP1, a secreted glycoprotein, as a metastatic driver and a potential candidate prognostic biomarker for lung metastasis in osteosarcoma patients. Osteosarcoma-derived secreted factors systemically reprogrammed the lung microenvironment and fostered a growth-permissive niche for incoming disseminated cells to survive and outgrow into overt metastasis. Daily administration of osteosarcoma cell secretome mimics the systemic release of tumour-secreted factors of a growing tumour in mice during PMN formation; Transcriptomic and histological analysis of premetastatic lungs revealed inflammatory-induced stromal fibroblast activation, neutrophil infiltration, and ECM remodelling as early onset pro-metastatic events; Proteome profiling identified EFEMP1, an extracellular secreted glycoprotein, as a potential predictive biomarker for lung metastasis and poor prognosis in osteosarcoma patients. Osteosarcoma patients with EFEMP1 expressing biopsies have a poorer overall survival.
Keyphrases
- early onset
- poor prognosis
- single cell
- small cell lung cancer
- squamous cell carcinoma
- end stage renal disease
- ejection fraction
- newly diagnosed
- long non coding rna
- late onset
- peritoneal dialysis
- prognostic factors
- stem cells
- bone marrow
- induced apoptosis
- physical activity
- metabolic syndrome
- extracellular matrix
- anti inflammatory
- type diabetes
- big data
- signaling pathway
- patient reported outcomes
- deep learning
- mesenchymal stem cells
- human health
- skeletal muscle
- ultrasound guided