The Heterogeneity of Osteosarcoma: The Role Played by Cancer Stem Cells
Osteosarcoma is the most common bone sarcoma and is one of the cancer entities characterized by the highest level of heterogeneity in humans. This heterogeneity takes place not only at the macroscopic and microscopic levels, with heterogeneous micro-envir
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The Heterogeneity of Osteosarcoma: The Role Played by Cancer Stem Cells Kristina Schiavone, Delphine Garnier, Marie-Francoise Heymann, and Dominique Heymann
Abstract Osteosarcoma is the most common bone sarcoma and is one of the cancer entities characterized by the highest level of heterogeneity in humans. This heterogeneity takes place not only at the macroscopic and microscopic levels, with heterogeneous micro-environmental components, but also at the genomic, transcriptomic and epigenetic levels. Recent investigations have revealed the existence in osteosarcoma of cancer cells with stemness properties. Cancer stem cells are characterized by their specific phenotype and low cycling capacity, and are linked to drug resistance, tumour growth and the metastatic process. In addition, cancer stem cells contribute to the enrichment of tumour heterogeneity. The present manuscript will describe the main characteristic features of cancer stem cells in osteosarcoma and will discuss their impact on maintaining tumour heterogeneity. Their clinical implications will also be briefly addressed. Keywords Tumour heterogeneity · Gene mutation drivers · Cancer stem-like cells · Circulating tumour cells · Monitoring · Clinical trials · Osteosarcoma · Cancer stem cell · Drug resistance · Cell dormancy
K. Schiavone INSERM, European Associated Laboratory “Sarcoma Research Unit”, Department of Oncology and Metabolism, Medical School, University of Sheffield, Sheffield, UK D. Garnier · M.-F. Heymann INSERM, Institut de Cancérologie de l’Ouest, CRCINA, Université de Nantes, Université d’Angers, Saint Herblain, France D. Heymann (*) INSERM, European Associated Laboratory “Sarcoma Research Unit”, Department of Oncology and Metabolism, Medical School, University of Sheffield, Sheffield, UK INSERM, Institut de Cancérologie de l’Ouest, CRCINA, Université de Nantes, Université d’Angers, Saint Herblain, France e-mail: [email protected] © Springer Nature Switzerland AG 2019 A. Birbrair (ed.), Stem Cells Heterogeneity in Cancer, Advances in Experimental Medicine and Biology 1139, https://doi.org/10.1007/978-3-030-14366-4_11
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11.1 Introduction Osteosarcoma is part of the family of malignant bone sarcomas which originate from a common mesenchymal precursor located in the bone marrow, and known as mesenchymal stem cells (Brown et al. 2018a). Osteosarcoma is the main bone sarcoma in adolescents and young adults, with a peak of incidence at around 18 years old. Osteosarcomas are preferentially detected in the metaphysis of long bones and the tumour tissue is characterized by the presence of osteoid matrix produced by cancer cells (Fig. 11.1). Microscopic heterogeneity is the first marker for osteosarcoma with the presence of highly vascularized, necrotic, proliferating and osteoid foci. Depending on the morphological features of the cancer cells, osteosarcomas can be classified as osteoblastic, chondroblastic, fibroblastic or telangiectatic. Current treatment combines neo-adjuvant chemotherapy, surge
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