Deciphering breast cancer treatment resistance remains hindered by the lack of models that can successfully capture the four-dimensional dynamics of the tumor microenvironment.Here,we show that microextrusion bioprint...Deciphering breast cancer treatment resistance remains hindered by the lack of models that can successfully capture the four-dimensional dynamics of the tumor microenvironment.Here,we show that microextrusion bioprinting can reproducibly generate distinct cancer and stromal compartments integrating cells relevant to human pathology.Our findings unveil the functional maturation of this millimeter-sized model,showcasing the development of a hypoxic cancer core and an increased surface proliferation.Maturation was also driven by the presence of cancer-associated fibroblasts(CAF)that induced elevated microvascular-like structures complexity.Such modulation was concomitant to extracellular matrix remodeling,with high levels of collagen and matricellular proteins deposition by CAF,simultaneously increasing tumor stiffness and recapitulating breast cancer fibrotic development.Importantly,our bioprinted model faithfully reproduced response to treatment,further modulated by CAF.Notably,CAF played a protective role for cancer cells against radiotherapy,facilitating increased paracrine communications.This model holds promise as a platform to decipher interactions within the microenvironment and evaluate stroma-targeted drugs in a context relevant to human pathology.展开更多
Sarcomas are a large family of cancers originating in the mesenchyme.Composed of more than 100 histological subtypes,soft tissue and bone sarcomas remain clinically challenging,particularly in children and adolescents...Sarcomas are a large family of cancers originating in the mesenchyme.Composed of more than 100 histological subtypes,soft tissue and bone sarcomas remain clinically challenging,particularly in children and adolescents in whom sarcomas are the second most common malignant entities.Osteosarcoma is the main primary bone tumor in adolescents and young adults and is characterized by a high propensity to induce distant metastatic foci and become multi-drug resistant.The innate and acquired resistance of osteosarcoma can be explained by high histological heterogeneity and genetic/molecular diversity.In the last decade,the notion of cancer stem-like cells(CSCs)has emerged.This subset of cancer cells has been linked to drug resistance properties,recurrence of the disease,and therapeutic failure.Although CSCs remain controversial,many elements are in favor of them playing a role in the development of the drug resistance profile.The present review gives a brief overview of the most recent biological evidence of the presence of CSCs in osteosarcomas and their role in the drug resistance profile of these rare oncological entities.Their use as promising therapeutic targets is discussed.展开更多
基金the financial support of INSERM(France)and"Fondation ARC pour la recherche sur le cancer".
文摘Deciphering breast cancer treatment resistance remains hindered by the lack of models that can successfully capture the four-dimensional dynamics of the tumor microenvironment.Here,we show that microextrusion bioprinting can reproducibly generate distinct cancer and stromal compartments integrating cells relevant to human pathology.Our findings unveil the functional maturation of this millimeter-sized model,showcasing the development of a hypoxic cancer core and an increased surface proliferation.Maturation was also driven by the presence of cancer-associated fibroblasts(CAF)that induced elevated microvascular-like structures complexity.Such modulation was concomitant to extracellular matrix remodeling,with high levels of collagen and matricellular proteins deposition by CAF,simultaneously increasing tumor stiffness and recapitulating breast cancer fibrotic development.Importantly,our bioprinted model faithfully reproduced response to treatment,further modulated by CAF.Notably,CAF played a protective role for cancer cells against radiotherapy,facilitating increased paracrine communications.This model holds promise as a platform to decipher interactions within the microenvironment and evaluate stroma-targeted drugs in a context relevant to human pathology.
基金supported by an internal ICO grant 2018(ref#“DorSarc-2018-ICO-DH”).
文摘Sarcomas are a large family of cancers originating in the mesenchyme.Composed of more than 100 histological subtypes,soft tissue and bone sarcomas remain clinically challenging,particularly in children and adolescents in whom sarcomas are the second most common malignant entities.Osteosarcoma is the main primary bone tumor in adolescents and young adults and is characterized by a high propensity to induce distant metastatic foci and become multi-drug resistant.The innate and acquired resistance of osteosarcoma can be explained by high histological heterogeneity and genetic/molecular diversity.In the last decade,the notion of cancer stem-like cells(CSCs)has emerged.This subset of cancer cells has been linked to drug resistance properties,recurrence of the disease,and therapeutic failure.Although CSCs remain controversial,many elements are in favor of them playing a role in the development of the drug resistance profile.The present review gives a brief overview of the most recent biological evidence of the presence of CSCs in osteosarcomas and their role in the drug resistance profile of these rare oncological entities.Their use as promising therapeutic targets is discussed.
