Establishment and Characterization of Cell Lines from Canine Metastatic Osteosarcoma. 2023

Ya-Ting Yang, and Alexander I Engleberg, and Vilma Yuzbasiyan-Gurkan
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.

Despite the advancements in treatments for other cancers, the outcomes for osteosarcoma (OSA) patients have not improved in the past forty years, especially in metastatic patients. Moreover, the major cause of death in OSA patients is due to metastatic lesions. In the current study, we report on the establishment of three cell lines derived from metastatic canine OSA patients and their transcriptome as compared to normal canine osteoblasts. All the OSA cell lines displayed significant upregulation of genes in the epithelial mesenchymal transition (EMT) pathway, and upregulation of key cytokines such as CXCL8, CXCL10 and IL6. The two most upregulated genes are MX1 and ISG15. Interestingly, ISG15 has recently been identified as a potential therapeutic target for OSA. In addition, there is notable downregulation of cell cycle control genes, including CDKN2A, CDKN2B and THBS1. At the protein level, p16INK4A, coded by CDKN2A, was undetectable in all the canine OSA cell lines, while expression of the tumor suppressor PTEN was variable, with one cell line showing complete absence and others showing low levels of expression. In addition, the cells express a variety of actionable genes, including KIT, ERBB2, VEGF and immune checkpoint genes. These findings, similar to those reported in human OSA, point to some genes that can be used for prognosis, targeted therapies and novel drug development for both canine and human OSA patients.

UI MeSH Term Description Entries
D001859 Bone Neoplasms Tumors or cancer located in bone tissue or specific BONES. Bone Cancer,Cancer of Bone,Cancer of the Bone,Neoplasms, Bone,Bone Neoplasm,Neoplasm, Bone
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D005809 Genes, Regulator Genes which regulate or circumscribe the activity of other genes; specifically, genes which code for PROTEINS or RNAs which have GENE EXPRESSION REGULATION functions. Gene, Regulator,Regulator Gene,Regulator Genes,Regulatory Genes,Gene, Regulatory,Genes, Regulatory,Regulatory Gene
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012516 Osteosarcoma A sarcoma originating in bone-forming cells, affecting the ends of long bones. It is the most common and most malignant of sarcomas of the bones, and occurs chiefly among 10- to 25-year-old youths. (From Stedman, 25th ed) Sarcoma, Osteogenic,Osteogenic Sarcoma,Osteosarcoma Tumor,Osteogenic Sarcomas,Osteosarcoma Tumors,Osteosarcomas,Sarcomas, Osteogenic,Tumor, Osteosarcoma,Tumors, Osteosarcoma
D016609 Neoplasms, Second Primary Abnormal growths of tissue that follow a previous neoplasm but are not metastases of the latter. The second neoplasm may have the same or different histological type and can occur in the same or different organs as the previous neoplasm but in all cases arises from an independent oncogenic event. The development of the second neoplasm may or may not be related to the treatment for the previous neoplasm since genetic risk or predisposing factors may actually be the cause. Neoplasms, Metachronous,Neoplasms, Metachronous Second Primary,Neoplasms, Therapy-Related,Neoplasms, Treatment-Related,Second Malignancy,Second Neoplasm,Second Primary Neoplasms,Therapy-Associated Neoplasms,Therapy-Related Cancer,Treatment-Associated Neoplasms,Treatment-Related Cancer,Cancer, Second Primary,Metachronous Neoplasms,Metachronous Second Primary Neoplasms,Neoplasms, Therapy-Associated,Neoplasms, Treatment-Associated,Second Cancer,Second Primary Neoplasms, Metachronous,Therapy-Associated Cancer,Therapy-Related Neoplasms,Treatment-Associated Cancer,Treatment-Related Neoplasms,Cancer, Second,Cancer, Therapy-Associated,Cancer, Therapy-Related,Cancer, Treatment-Associated,Cancer, Treatment-Related,Cancers, Second,Cancers, Second Primary,Cancers, Therapy-Associated,Cancers, Therapy-Related,Cancers, Treatment-Associated,Cancers, Treatment-Related,Malignancies, Second,Malignancy, Second,Metachronous Neoplasm,Neoplasm, Metachronous,Neoplasm, Second,Neoplasm, Second Primary,Neoplasm, Therapy-Associated,Neoplasm, Therapy-Related,Neoplasm, Treatment-Associated,Neoplasm, Treatment-Related,Neoplasms, Second,Neoplasms, Therapy Associated,Neoplasms, Therapy Related,Neoplasms, Treatment Associated,Neoplasms, Treatment Related,Second Cancers,Second Malignancies,Second Neoplasms,Second Primary Cancer,Second Primary Cancers,Second Primary Neoplasm,Therapy Associated Cancer,Therapy Associated Neoplasms,Therapy Related Cancer,Therapy Related Neoplasms,Therapy-Associated Cancers,Therapy-Associated Neoplasm,Therapy-Related Cancers,Therapy-Related Neoplasm,Treatment Associated Cancer,Treatment Associated Neoplasms,Treatment Related Cancer,Treatment Related Neoplasms,Treatment-Associated Cancers,Treatment-Associated Neoplasm,Treatment-Related Cancers,Treatment-Related Neoplasm
D050756 Cyclin-Dependent Kinase Inhibitor Proteins A group of cell cycle proteins that negatively regulate the activity of CYCLIN/CYCLIN-DEPENDENT KINASE complexes. They inhibit CELL CYCLE progression and help control CELL PROLIFERATION following GENOTOXIC STRESS as well as during CELL DIFFERENTIATION. CIP-KIP Cyclin-Dependent Kinase Inhibitors,INK4 Cyclin-Dependent Kinase Inhibitors,CDKI Proteins,CIP-KIP CDKI Proteins,CIP-KIP CKI Proteins,CKI Proteins,Cyclin-Kinase Inhibitor Proteins,INK4 CDKI Proteins,INK4 CKI Proteins,Inhibitors of Cyclin-Dependent Kinase 4 Proteins,CDKI Proteins, CIP-KIP,CDKI Proteins, INK4,CIP KIP CDKI Proteins,CIP KIP CKI Proteins,CIP KIP Cyclin Dependent Kinase Inhibitors,CKI Proteins, CIP-KIP,CKI Proteins, INK4,Cyclin Dependent Kinase Inhibitor Proteins,Cyclin Kinase Inhibitor Proteins,INK4 Cyclin Dependent Kinase Inhibitors,Inhibitor Proteins, Cyclin-Kinase,Inhibitors of Cyclin Dependent Kinase 4 Proteins

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