Stem cell factor enhances the adhesion of AML cells to fibronectin and augments fibronectin-mediated anti-apoptotic and proliferative signals
Stem cell factor enhances the adhesion of AML cells to fibronectin and augments fibronectin-mediated anti-apoptotic and proliferative signals
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DOI：
10.1038/sj.leu.2401136
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发表时间：
1998-09-01
期刊：
影响因子：
11.4
通讯作者：
Gottlieb, DJ
中科院分区：
文献类型：
--
作者：
Bendall, LJ;Makrynikola, V;Gottlieb, DJ
急性髓系白血病(AML)细胞在其细胞表面表达SCF受体c-kit(CD117)，并在暴露于干细胞因子(SCF)后增强与纤维连接蛋白(FN)的黏附。黏附增强发生在5分钟内，呈剂量依赖关系，持续时间超过2小时。AML细胞表达的表面FN受体非常晚期抗原-5(VLA-8，CD49e/CD29)是通过表达VLA-8，CD49e/CD29来实现的。FN对未受刺激的AML细胞的凋亡率低于对照组(抑制率为22.5+/-7.0%，P=0.02，n=8)。单独暴露于无FN的SCF也可抑制AML细胞的凋亡(与对照组相比，下降19.0+/-7.7%，P=0.06，n=8)。同时加入SCF和FN后，AML细胞的凋亡率增加到37.8+/-7.9%(与对照组相比P=0.005，与FN单独作用相比P=0.04，与SCF单独作用相比P=0.06)，表明SCF不仅增强了AML细胞黏附FN的倾向，而且还增加了FN接触后的存活益处。部分(但不是全部)细胞凋亡的减少是通过VLA-5介导的。SCF和FN的联合应用也会影响AML细胞的增殖，在所研究的半数病例中，SCF和FN对AML细胞的增殖有协同作用。以CD34(+)人正常造血祖细胞为研究对象，FN对其凋亡影响不大，也不能增强SCF的抗凋亡作用。然而，它与SCF在促进CD34(+)细胞增殖方面确实有协同作用。AML细胞暴露在SCF和FN中，两者都可以在骨髓基质中发现高浓度，抑制细胞凋亡。细胞因子和细胞外基质蛋白相互增强彼此的作用，因为干细胞因子增强了与纤维连接蛋白的黏附，进而增强了细胞因子单独传递的生存信号。细胞因子和黏附受体可以结合在一起影响细胞的特性，包括增殖和存活。
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-8, 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.