Evidence for the osteosarcoma stem cell

Abstract

Osteosarcoma is a highly malignant bone tumor of children and young adults. Cytotoxic chemotherapy combined with aggressive surgery only has a 60% survival rate. Historically, chemotherapy has been developed assuming that all cells within a particular cancer are clonal and near identical. Appreciating the now apparent functional heterogeneity of osteosarcoma cells within and between individual tumors will likely be critical in developing much needed novel effective therapies. The foundation for this heterogeneity may lie in the so called “cancer stem cell” or tumorigenic cell of origin. In this brief review, we will examine the evidence for the existence of this cell and its potential importance for future therapies.

Sox2 antagonizes the Hippo pathway to maintain stemness in cancer cells

“…It is interesting to note that Sox2 is generally thought to act in synergy with other transcription factors, which bind near the Sox2-binding site, the best known case being the Sox2/Oct4 interaction, which governs the expression of many ES cell genes 65 . Although expression of Oct4 in osteosarcoma cells has been reported, this finding does not appear reproducible 43 . We have never been able to detect Oct4 expression in the osteoblast lineage or in osteosarcomas, thus the manner by which Sox2 activates or represses gene transcription in these cells may require an interaction with multiple cofactors.…”

“…This is not simply a reflection of the stem-like nature of these cells as other stem cell transcription factors (for example, Oct4) are not expressed in CSC from osteosarcomas 43 . It is therefore of great interest to understand not only how the expression of this stem cell transcription factor is maintained or activated in CSC, but also the mechanisms by which Sox2 expression induces or maintains a CSC phenotype.…”

Perspectives on cancer stem cells in osteosarcoma

“…Clonal isolates of GFP+ cells were highly tumorigenic compared to the rest of the population. While these studies suggest a correlation between expression of these pluripotency genes and stemness, a serious caveat in the OCT4-GFP experiments is the inability to detect authentic endogenous OCT4 expression [57]. …”

Doxorubicin activates the Notch signaling pathway in osteosarcoma

“…Various factors contribute to this heterogeneic response, in which cell hierarchy plays an important role. A number of reports have identified the existence of osteosarcoma stem cells, a subpopulation of cells that possess the capacity to self-renew and multi-differentiate (7)(8)(9). In addition, cancer stem cells participate in drug resistance, thus contributing to treatment failure (10,11).…”