Dao T, Holán V, Minowada J
Fujisaki Cell Center, Hayashibara Biochemical Laboratories, Inc., Okayama, Japan.
Neoplasma. 1993;40(5):265-73.
A novel leukemia cell growth-promoting activity has been identified in the culture supernatant from a human B cell leukemia cell line, BALL-1. The supernatant from unstimulated cultures of the BALL-1 cells significantly promoted the growth of 16 out of 24 leukemia/lymphoma cell lines of different lineages (T, B and non-lymphoid) in a minimal concentration of fetal bovine serum (FBS), and of 5 out of 12 cases of fresh leukemia cells in FBS-free medium. The growth-promoting activity in the BALL-1 supernatant has been further characterized using FPLC chromatography, molecular weight (MW) sieve filtration and dialysis. The MW of the factor was less than 10 kDa. The growth-promoting activity was heat and acid stable and resistant to trypsin treatment. The factor isolated from the BALL-1 supernatant was distinct from known polypeptide growth factors with MW below 10 kDa, such as epidermal growth factor, transforming growth factor alpha, insulin-like growth factor I (IGF-I), IGF-II and insulin, as determined by specific antibodies and by cell growth-promoting tests. The factor in the BALL-1 supernatant did not promote the proliferation of normal human fresh peripheral blood lymphocytes or mouse fibroblast cell line, BALB/c3T3. In addition to the BALL-1 supernatant, a similar growth-promoting activity was found in the culture supernatants from 13 of 17 leukemia/lymphoma cell lines tested. The activity in these culture supernatants promoted the growth of leukemia/lymphoma cell lines in autocrine and/or paracrine fashions. These observations suggest that the low MW cell growth-promoting activity found in the BALL-1 culture supernatant is mediated by a novel factor which may well be responsible for the clonal expansion of particular leukemic clones.
在人B细胞白血病细胞系BALL-1的培养上清液中,已鉴定出一种新型的白血病细胞生长促进活性。在最低浓度胎牛血清(FBS)条件下,BALL-1细胞未受刺激培养的上清液显著促进了24种不同谱系(T、B和非淋巴细胞)白血病/淋巴瘤细胞系中的16种的生长,并且在无FBS培养基中促进了12例新鲜白血病细胞中的5例的生长。利用快速蛋白质液相色谱(FPLC)、分子量(MW)筛过滤和透析对BALL-1上清液中的生长促进活性进行了进一步表征。该因子的分子量小于10 kDa。生长促进活性对热和酸稳定,且对胰蛋白酶处理具有抗性。通过特异性抗体和细胞生长促进试验确定,从BALL-1上清液中分离出的因子不同于已知的分子量低于10 kDa的多肽生长因子,如表皮生长因子、转化生长因子α、胰岛素样生长因子I(IGF-I)、IGF-II和胰岛素。BALL-1上清液中的因子不会促进正常人新鲜外周血淋巴细胞或小鼠成纤维细胞系BALB/c3T3的增殖。除了BALL-1上清液外,在17种测试的白血病/淋巴瘤细胞系中的13种的培养上清液中也发现了类似的生长促进活性。这些培养上清液中的活性以自分泌和/或旁分泌方式促进白血病/淋巴瘤细胞系的生长。这些观察结果表明,在BALL-1培养上清液中发现的低分子量细胞生长促进活性是由一种新型因子介导的,该因子很可能是特定白血病克隆克隆性扩增的原因。