Tumourigenic canine osteosarcoma cell lines associated with frizzled‐6 up‐regulation and enhanced side population cell frequency

  title={Tumourigenic canine osteosarcoma cell lines associated with frizzled‐6 up‐regulation and enhanced side population cell frequency},
  author={Lucas Campos de S{\'a} Rodrigues and Katie E Holmes and Victoria Thompson and Michael A. Newton and Timothy J. Stein},
  journal={Veterinary and Comparative Oncology},
An increased serum alkaline phosphatase concentration is known to be associated with a negative prognosis in canine and human osteosarcoma. To expand upon previous studies regarding the biological relevance of increased serum alkaline phosphatase as a negative prognostic factor, xenogeneic heterotopic transplants were performed using six canine primary osteosarcoma cell lines generated from patients with differing serum alkaline phosphatase concentrations (three normal and three increased… 
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The Association of Endothelin‐1 Signaling with Bone Alkaline Phosphatase Expression and Protumorigenic Activities in Canine Osteosarcoma
Increases in bone alkaline phosphatase activity are associated with osteoblastic OS lesions, and might be an epiphenomenon of active endothelin‐1 signaling or excessive osteoproduction within the localized bone microenvironment.
A systems medicine approach for finding target proteins affecting treatment outcomes in patients with non-Hodgkin lymphoma
The results revealed that the most PR-specific proteins were associated with events involved in tumor development, while chemotherapy in the PS group was associated with side effects of drugs and/or cancer recurrence.
Canine sarcomas as a surrogate for the human disease
A description of the incidence, pathology, molecular characteristics and previous translational therapeutic studies associated with these naturally occurring canine sarcomas holds great promise for effective incorporation into drug development schemas, for evaluation of target modulation or other pharmacodynamic measures associated with therapeutic response.


Canine osteosarcoma cell lines from patients with differing serum alkaline phosphatase concentrations display no behavioural differences in vitro.
To determine whether in vitro behaviour differs between primary osteosarcoma cell lines generated from patients with normal or increased serum ALP, assays were performed to evaluate proliferation, migration, invasion and chemosensitivity.
β-Catenin transcriptional activity is minimal in canine osteosarcoma and its targeted inhibition results in minimal changes to cell line behaviour.
Results suggest canonical Wnt signalling is minimally active in canine OS and its targeted inhibition is not a relevant therapeutic strategy.
Global Gene Expression Analysis of Canine Osteosarcoma Stem Cells Reveals a Novel Role for COX-2 in Tumour Initiation
The successful isolation of CSCs from primary canine osteosarcoma, as well as established cell lines, are reported, showing that these cells can form tumourspheres, and demonstrate relative resistance to chemotherapy.
Genes Regulated in Metastatic Osteosarcoma: Evaluation by Microarray Analysis in Four Human and Two Mouse Cell Line Systems
The results imply an OS phenotype specific expression pattern of metastasis regulating proteins and form a basis for further investigation of gene expression profiles in patients' samples combined with survival analysis with the aim to optimize treatment strategies to develop new drugs and to improve the survival of patients with the most common form of osteoblastic OS.
Characterization of β-catenin expression in canine osteosarcoma.
Results indicate β-catenin is frequently expressed within the cytoplasm of neoplastic cells in canine OSA but contains no detectable mutations in exon 3, similar to human OSA.
Frizzled receptor 6 marks rare, highly tumourigenic stem-like cells in mouse and human neuroblastomas
It is shown that expression of one Wnt receptors, Fzd6, predicts poor survival in neuroblastoma patients and marks rare, HIF1/2 α-positive cells in tumour hypoxic areas, and is a new surface marker of aggressive neuro Blastoma cells with stem cell-like features.
Therapeutic implications of an enriched cancer stem-like cell population in a human osteosarcoma cell line
MNNG/HOS osteosarcoma cells contain a stem-like cell population relatively resistant to conventional chemotherapeutic agents and irradiation, which appears to be related with some stem features, namely the high expression of the drug efflux transporters P-glycoprotein and BCRP and their quiescent nature, which may provide a biological basis for resistance to therapy and recurrence commonly observed in osteosARcoma.
Side population cells have the characteristics of cancer stem-like cells/cancer-initiating cells in bone sarcomas
The identified and characterised side population (SP) cells that showed drug-resistant features in human bone sarcoma cell lines and showed cancer-initiating ability in vitro and in vivo and could serve as candidate markers for CSCs in bone Sarcomas.
Comparison of Gene Expression Profiling in Sarcomas and Mesenchymal Stem Cells Identifies Tumorigenic Pathways in Chemically Induced Rat Sarcoma Model
The current study indicated that these rat sarcomas could be a good model for their human counterparts and will provide the further insights into the molecular pathways and mechanisms involved in sarcoma pathogenesis.
Flow cytometric techniques for detection of candidate cancer stem cell subpopulations in canine tumour models.
Primary cells may provide a more rewarding model for studying tumour heterogeneity in the context of CSC, and it will be essential to fully characterize any candidate subpopulations to ensure that they meet CSC criteria.