Overcoming Therapeutic Resistance of Bone Sarcomas: Overview of the Molecular Mechanisms and Therapeutic Targets for Bone Sarcoma Stem Cells

Table 1

Markers of bone sarcoma stem cells.

Subtype	Marker	Function, clinical relevance	Reference
Osteosarcoma	Sarcosphere	Drug resistance, overexpressing Oct3/4, Nanog, and Stat3	[16–19]
	CD133	Sphere formation, multipotency, tumorigenicity, self-renewal, inclusion of SP cells, overexpressing Oct3/4 and Nanog	[24–26]
	/CD49	Sphere formation, migration, invasion, tumorigenicity, lung metastasis	[28]
	/CD44	Sphere formation, migration, invasion, tumorigenicity, lung metastasis	[27]
	CD117/Stro-1	Drug resistance, invasion, metastasis, tumorigenicity, self-renewal, overexpressing ABCG2 and CXCR4	[25, 41]
	SP	Drug resistance, self-renewal, tumorigenicity	[34, 35]
	/CD248	Tumorigenicity, invasion	[40]
	ALDH	Proliferation, tumorigenicity, overexpressing Oct3/4, Nanog, Sox2, and Stat3	[47, 48]
	CBX3 and ABCA5	Highly expressed in spheres	[49]
	CD47	Invasion, blockage of macrophage phagocytosis, prognostic value	[52]
	CD271	Self-renewal, differentiation, drug resistance, tumorigenicity, overexpressing Oct3/4, Nanog, Stat3, Bcl-2, and ABCG2	[54]
	Oct3/4	Tumorigenicity, self-renewal	[57, 58]
	Sox2	Soft agar growth, migration, invasion, tumorigenicity, reduced Wnt signaling	[59]
Ewing sarcoma	Sarcosphere	Drug resistance, overexpressing Oc3/4, Nanog, Stat3, Sox2, Sox 10, and EWS-FLI1, fail to self-renew and enhance tumorigenicity	[19, 20]
	CD133	Sphere formation, multipotency, tumorigenicity, overexpressing Oct3/4 and Nanog, no difference in drug resistance and tumorigenicity	[29, 30]
	CD57	Migration, invasion, multipotency, tumorigenicity, no correlation with CD133	[55]
	SP	Drug resistance, clonogenicity, invasion, asymmetric division	[33, 36, 37]
	ALDH	Clonogenicity, sphere formation, tumorigenicity, drug resistance	[46]
Chondrosarcoma	Sarcosphere	Multipotency, overexpressing Oct3/4, Nanog, and Stat3, expressing Stro-1, CD44, and CD105	[16]
	CD133	Tumorigenicity	[25]
	SP	NA	[34]

SP: side population; ALDH: aldehyde dehydrogenase; NA: not available.