Figure 4. CD49f⁻ cells with greater tumorigenicity and drug resistance generate CD49f⁺ subpopulation.

(A) CD49f⁻ cells differentiated to CD49f⁺ subpopulation in culture (9.78%; left panel) and in NOD/SCID mice (>89%, right panel). (B) Both CD49f⁻ and CD49f⁺ cells isolated from UT2 (left panel) or KHOS/NP cells (right panel) showed osteogenic and adipogenic potential, as judged by ARS and ORO staining. Cross staining was used as negative control (sections 1, 2 vs. 3, 4; sections 5, 6 vs. 7, 8). (C) CD49f⁻ cells showed greater tumorigenicity than CD49f⁺ cells. (D) The CD49f⁺ subpopulation was decreased in UT2 and primary osteosarcoma TTC606 cells treated with cisplatin or doxorubicin. (E & F) CD49f⁻ subpopulation isolated from UT2 (panel E) or TTC606 cells (panel F) resisted cisplatin treatment. Percentages of surviving cells were shown relative to the IC₅₀ value for each of cell populations. (G) IC₅₀ values for CD49f⁺ or CD49f⁻ cells treated with different drugs for 48 hr. Data are means with 95% confidence intervals.