Dataset Information

Cancer stem cells from human glioblastoma resemble but do not mimic original tumors after in vitro passaging in serum-free media.

ABSTRACT: Human gliomas harbour cancer stem cells (CSCs) that evolve along the course of the disease, forming highly heterogeneous subpopulations within the tumour mass. These cells possess self-renewal properties and appear to contribute to tumour initiation, metastasis and resistance to therapy. CSC cultures isolated from surgical samples are considered the best preclinical in vitro model for primary human gliomas. However, it is not yet well characterized to which extent their biological and functional properties change during in vitro passaging in the serum-free culture conditions. Here, we demonstrate that our CSC-enriched cultures harboured from one to several CSC clones from the human glioma sample. When xenotransplanted into mouse brain, these cells generated tumours that reproduced at least three different dissemination patterns found in original tumours. Along the passages in culture, CSCs displayed increased expression of stem cell markers, different ratios of chromosomal instability events, and a varied response to drug treatment. Our findings highlight the need for better characterization of CSC-enriched cultures in the context of their evolution in vitro, in order to uncover their full potential as preclinical models in the studies aimed at identifying molecular biomarkers and developing new therapeutic approaches of human gliomas.

SUBMITTER: Garcia-Romero N

PROVIDER: S-EPMC5323200 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Cancer stem cells from human glioblastoma resemble but do not mimic original tumors after in vitro passaging in serum-free media.

García-Romero Noemí N González-Tejedo Carmen C Carrión-Navarro Josefa J Esteban-Rubio Susana S Rackov Gorjana G Rodríguez-Fanjul Vanessa V Oliver-De La Cruz Jorge J Prat-Acín Ricardo R Peris-Celda María M Blesa David D Ramírez-Jiménez Laura L Sánchez-Gómez Pilar P Perona Rosario R Escobedo-Lucea Carmen C Belda-Iniesta Cristobal C Ayuso-Sacido Angel A

Oncotarget 20161001 40

Human gliomas harbour cancer stem cells (CSCs) that evolve along the course of the disease, forming highly heterogeneous subpopulations within the tumour mass. These cells possess self-renewal properties and appear to contribute to tumour initiation, metastasis and resistance to therapy. CSC cultures isolated from surgical samples are considered the best preclinical in vitro model for primary human gliomas. However, it is not yet well characterized to which extent their biological and functional ...[more]

PMID: 27589567

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Project description:Pancreatic ductal adenocarcinoma (PDAC) is almost universally fatal, in large part due to a protective fibrotic barrier generated by tumor-associated stromal (TAS) cells. This barrier is thought to promote cancer cell survival and confounds attempts to develop effective therapies. We present a 3D in vitro system that replicates the mechanical properties of the PDAC microenvironment, representing an invaluable tool for understanding the biology of the disease. Mesoscale indentation quantified viscoelastic metrics of resected malignant tumors, inflamed chronic pancreatitis regions, and histologically normal tissue. Both pancreatitis (2.15?±?0.41?kPa, Mean?±?SD) and tumors (5.46?±?3.18?kPa) exhibit higher Steady-State Modulus (SSM) than normal tissue (1.06?±?0.25?kPa; p?<?.005). The average viscosity of pancreatitis samples (63.2?±?26.7?kPa·s) is significantly lower than that of both normal tissue (252?±?134?kPa·s) and tumors (349?±?222?kPa·s; p?<?.005). To mimic this remodeling behavior, PDAC and TAS cells were isolated from human PDAC tumors. Conditioned medium from PDAC cells was used to culture TAS-embedded collagen hydrogels. After 7?days, TAS-embedded gels in control medium reached SSM (1.45?±?0.12?kPa) near normal pancreas, while gels maintained with conditioned medium achieved higher SSM (3.38?±?0.146?kPa) consistent with tumors. Taken together, we have demonstrated an in vitro system that recapitulates in vivo stiffening of PDAC tumors. In addition, our quantification of viscoelastic properties suggests that elastography algorithms incorporating viscosity may be able to more accurately distinguish between pancreatic cancer and pancreatitis. STATEMENT OF SIGNIFICANCE:Understanding tumor-stroma crosstalk in pancreatic ductal adenocarcinoma (PDAC) is challenged by a lack of stroma-mimicking model systems. To design appropriate models, pancreatic tissue must be characterized with a method capable of evaluating in vitro models as well. Our indentation-based characterization tool quantified the distinct viscoelastic signatures of inflamed resections from pancreatitis, tumors from PDAC, and otherwise normal tissue to inform development of mechanically appropriate engineered tissues and scaffolds. We also made progress toward a 3D in vitro system that recapitulates mechanical properties of tumors. Our in vitro model of stromal cells in collagen and complementary characterization system can be used to investigate mechanisms of cancer-stroma crosstalk in PDAC and to propose and test innovative therapies.

Dataset Information

Cancer stem cells from human glioblastoma resemble but do not mimic original tumors after in vitro passaging in serum-free media.

Publications

Cancer stem cells from human glioblastoma resemble but do not mimic original tumors after in vitro passaging in serum-free media.

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