Bendall L J, Makrynikola V, Hutchinson A, Bianchi A C, Bradstock K F, Gottlieb D J
Department of Haematology, University of Sydney at Westmead Hospital, Sydney, NSW, Australia.
Leukemia. 1998 Sep;12(9):1375-82. doi: 10.1038/sj.leu.2401136.
Acute myeloid leukaemia (AML) cells express the SCF receptor c-kit (CD117) on their cell surface and demonstrate enhanced adhesion to fibronectin (FN) following exposure to stem cell factor (SCF). Increased adhesion occurs within 5 min, is dose dependent, and persists beyond 2 h. Baseline and enhanced adhesion occur through the surface FN receptor very late antigen-5 (VLA-5, CD49e/CD29) which is expressed by AML cells. Unstimulated AML cells exposed to FN undergo less apoptosis than controls (inhibition 22.5 +/- 7.0%, P = 0.02, n = 8). Exposure to SCF alone without FN also inhibits AML cell apoptosis (by 19.0 +/- 7.7% compared to controls, P = 0.06, n = 8). Simultaneous exposure to SCF and FN increases the inhibition of AML cell apoptosis to 37.8 +/- 7.9% (P = 0.005 compared to control, P = 0.04 compared to FN alone, P = 0.06 compared to SCF alone) demonstrating that SCF not only enhances the propensity of AML cells to adhere to FN, but also results in an additive survival benefit following FN contact. Some but not all the reduction in apoptosis is mediated through VLA-5. The combination of SCF and FN also affects proliferation, resulting in a synergistic enhancement of AML cell proliferation in half the cases studied. When normal CD34+ human haemopoietic progenitors were studied, FN had little effect on their apoptosis and failed to enhance the anti-apoptotic effect of SCF. It did, however, synergise with SCF in promoting CD34+ cell proliferation. Exposure of AML cells to SCF and FN, both of which can be found in high concentration in the bone marrow stroma, inhibits apoptosis. Cytokines and extracellular matrix proteins augment each others' effects since SCF enhances adhesion to fibronectin, which in turn augments the survival signal delivered by the cytokine alone. Cytokine and adhesion receptors can combine to affect cell characteristics including proliferation and survival.
急性髓系白血病（AML）细胞在其细胞表面表达干细胞因子（SCF）受体c-kit（CD117），并且在暴露于SCF后对纤连蛋白（FN）的黏附增强。黏附增强在5分钟内发生，呈剂量依赖性，并且持续超过2小时。基线黏附和增强黏附通过AML细胞表达的表面FN受体极迟抗原-5（VLA-5，CD49e/CD29）发生。暴露于FN的未受刺激的AML细胞比对照经历更少的凋亡（抑制率22.5±7.0%，P = 0.02，n = 8）。单独暴露于SCF而无FN也抑制AML细胞凋亡（与对照相比为19.0±7.7%，P = 0.06，n = 8）。同时暴露于SCF和FN将AML细胞凋亡的抑制率提高到37.8±7.9%（与对照相比P = 0.005，与单独FN相比P = 0.04，与单独SCF相比P = 0.06），表明SCF不仅增强AML细胞黏附FN的倾向，而且在接触FN后还产生额外的生存益处。部分但并非全部凋亡减少是通过VLA-5介导的。SCF和FN的组合也影响增殖，在半数研究病例中导致AML细胞增殖的协同增强。当研究正常的CD34+人造血祖细胞时，FN对其凋亡几乎没有影响，并且未能增强SCF的抗凋亡作用。然而，它在促进CD34+细胞增殖方面与SCF协同作用。AML细胞暴露于SCF和FN（两者在骨髓基质中均可高浓度发现）会抑制凋亡。细胞因子和细胞外基质蛋白相互增强彼此的作用，因为SCF增强对纤连蛋白的黏附，这反过来又增强了单独细胞因子传递的生存信号。细胞因子和黏附受体可以结合起来影响包括增殖和生存在内的细胞特性。
