Breast cancer is marked by large increases in the protein fibers around tumor cells.These fibers increase the mechanical stiffness of the tissue,which has long been used for tumor diagnosis by manual palpation.Recent ...Breast cancer is marked by large increases in the protein fibers around tumor cells.These fibers increase the mechanical stiffness of the tissue,which has long been used for tumor diagnosis by manual palpation.Recent research in bioengineering has led to the development of novel biomaterials that model the mechanical and architectural properties of the tumor microenvironment and can be used to understand how these cues regulate the growth and spread of breast cancer.Herein,we provide an overview of how the mechanical properties of breast tumor tissues differ from those of normal breast tissue and noncancerous lesions.We also describe how biomaterial models make it possible to understand how the stiffness and viscosity of the extracellular environment regulate cell migration and breast cancer metastasis.We highlight the need for biomaterial models that allow independent analysis of the individual and different mechanical properties of the tumor microenvironment and that use cells derived from different regions within tumors.These models will guide the development of novel mechano-based therapies against breast cancer metastasis.展开更多
Aims:Circulating tumour cells(CTCs)can be detected in peripheral blood using their physical properties(increased size and less deformable than normal circulating blood cells)or using cell surface markers.The study of ...Aims:Circulating tumour cells(CTCs)can be detected in peripheral blood using their physical properties(increased size and less deformable than normal circulating blood cells)or using cell surface markers.The study of these CTCs should provide important insights into tumour biology,including mechanisms of drug resistance.We performed a pilot study(IRAS ID:235459)to evaluate if CTCs could be isolated from peripheral blood samples collected from soft tissue sarcoma(STS)patients.Methods:We used a combined approach that first enriched samples for CTCs using a microfluidic cassette via ParosrtixTMPR1,and then sorted cells stained for vimentin and cytokeratin using the DEPArrayTM.The total circulating cell-free DNA(cfDNA)level was also analysed.Data were correlated with clinical parameters.Results:13 patients were recruited to this study:7 patients with localised disease and 6 patients with metastatic disease.CTCs exhibited a high heterogeneity based on their expression of mesenchymal and epithelial markers.There was no significant difference in the number of CTCs between patients with localised versus metastatic disease.We observed no correlation between CTC numbers and cfDNA;however,the number of CTCs did correlate with primary tumour size.Conclusion:The present study demonstrates the presence of CTCs in STS patients with localised and advanced disease.Further and larger studies are needed to characterise STS CTCs and to evaluate their prognostic significance.展开更多
基金The authors would like to thank the Weston Park Cancer Centre(University of Sheffield,UK)the Fundação para a Ciência e a Tecnologia(FCT),the Portuguese Government(PEst-OE/QUI/UI0674/2013)the Agência Regional para o Desenvolvimento da InvestigaçaõTecnologia e Inovação(ARDITI),M1420-01-0145-FEDER-000005 Centro de Química da Madeira(CQM)(Madeira 14-20).
文摘Breast cancer is marked by large increases in the protein fibers around tumor cells.These fibers increase the mechanical stiffness of the tissue,which has long been used for tumor diagnosis by manual palpation.Recent research in bioengineering has led to the development of novel biomaterials that model the mechanical and architectural properties of the tumor microenvironment and can be used to understand how these cues regulate the growth and spread of breast cancer.Herein,we provide an overview of how the mechanical properties of breast tumor tissues differ from those of normal breast tissue and noncancerous lesions.We also describe how biomaterial models make it possible to understand how the stiffness and viscosity of the extracellular environment regulate cell migration and breast cancer metastasis.We highlight the need for biomaterial models that allow independent analysis of the individual and different mechanical properties of the tumor microenvironment and that use cells derived from different regions within tumors.These models will guide the development of novel mechano-based therapies against breast cancer metastasis.
基金supported by Sarcoma UK(Grant number:SUK02.2017)sponsored by Sheffield Teaching Hospitals NHS Foundation Trust(STH:19860).
文摘Aims:Circulating tumour cells(CTCs)can be detected in peripheral blood using their physical properties(increased size and less deformable than normal circulating blood cells)or using cell surface markers.The study of these CTCs should provide important insights into tumour biology,including mechanisms of drug resistance.We performed a pilot study(IRAS ID:235459)to evaluate if CTCs could be isolated from peripheral blood samples collected from soft tissue sarcoma(STS)patients.Methods:We used a combined approach that first enriched samples for CTCs using a microfluidic cassette via ParosrtixTMPR1,and then sorted cells stained for vimentin and cytokeratin using the DEPArrayTM.The total circulating cell-free DNA(cfDNA)level was also analysed.Data were correlated with clinical parameters.Results:13 patients were recruited to this study:7 patients with localised disease and 6 patients with metastatic disease.CTCs exhibited a high heterogeneity based on their expression of mesenchymal and epithelial markers.There was no significant difference in the number of CTCs between patients with localised versus metastatic disease.We observed no correlation between CTC numbers and cfDNA;however,the number of CTCs did correlate with primary tumour size.Conclusion:The present study demonstrates the presence of CTCs in STS patients with localised and advanced disease.Further and larger studies are needed to characterise STS CTCs and to evaluate their prognostic significance.
