Abstract
A number of solid tumors contain a distinct subpopulation of cells, termed cancer stem cells (CSCs) which represent the source for tissue renewal and hold malignant potential and which would be responsible for therapy resistance. Today, the winning goal in cancer research would be to find drugs to kill both cancer cells and cancer stem cells, while sparing normal cells. Osteosarcoma is an aggressive pediatric tumor of growing bones that, despite surgery and chemotherapy, is prone to relapse. We have recently selected from human osteosarcoma MG63 cells a cancer stem-like cell line (3AB-OS), which has unlimited proliferative potential, high levels of stemness-related markers, and in vivo tumorforming capacity in xenograft assays. Here, we have shown that 3AB-OS cells can differentiate in vitro into endoderm-, mesoderm-and ectoderm-derived lineages. Cell differentiation is morphological, molecular and functional. We propose that this model system of 3AB-OS differentiation in vitro might have a number of useful purposes, among which the study of molecular mechanisms of osteosarcoma origin, and the analysis of factors involved in specification of the various cell lineages. We still do not know either what are the shared and distinguishing characters between CSCs and normal stem cells, or what is the reason why the cancer stem cells, like the normal stem cells, have the ability to differentiate toward the derivatives of the primary germ layers. It is possible that each of the differentiation capability may be exploited by CSCs to supply their needs of growing and surviving in hostile microenvironment.
Highlights
Osteosarcoma is the most common non-hematologic malignancy of bone in children and adults, consisting of malignant cells that produce immature bone and is characterized by osteoid formation within the tumor [1,2]
It is well known that cancer stem cells (CSCs) are cells that possess the capacity to self-renew and to give rise to the heterogeneous lineages of cancer cells that comprise the tumor, which can self-renew and undergo asymmetrical divisions, giving rise to a differentiated progeny that represents most of the tumor populations [32]
CSCs possess the ability for prolonged survival, angiogenesis, and high resistance to chemotherapy and radiotherapy, which could explain the high frequency of neoplasia relapse years after apparently eradicating therapies [5]
Summary
Osteosarcoma is the most common non-hematologic malignancy of bone in children and adults, consisting of malignant cells that produce immature bone and is characterized by osteoid formation within the tumor [1,2]. There are about 2500 new cases of osteosarcoma diagnosed each year in the US with about one half occurring in children and adolescents, younger than 20 years of age. It is a highly aggressive tumor exhibiting clinical, histologic, and molecular heterogeneity. The tumor, which in about 80% of cases occurs at sites of rapid bone growth (the metaphyses of long bones), has an initial peak incidence in the pediatric and early adult population and a second peak incidence in later adult life [3]. R. Di Fiore et al / Stem Cell Discovery 3 (2013) 188-201 coma patients without metastasis, and there is no established second-line chemotherapy for relapsed osteosarcoma [4]. There is an urgent need to identify new therapeutic strategies to improve the clinical outcome of patients with osteosarcoma
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