Arteaga C L, Hanauske A R, Clark G M, Osborne C K, Hazarika P, Pardue R L, Tio F, Von Hoff D D
University of Texas Health Science Center, San Antonio, Division of Medical Oncology 78284.
Cancer Res. 1988 Sep 1;48(17):5023-8.
alpha Transforming growth factors (alpha-TGFs) are polypeptides that stimulate anchorage-independent growth of various nontransformed cells in vitro and are believed to be involved in autocrine stimulation of tumor cells. alpha-TGF activity is secreted by a variety of human cancers leading to the possibility that it may serve as a tumor marker. alpha-TGF activity was measured in 130 effusions from patients with various types of cancer with a radioimmunoassay using sheep antibodies against the C-terminal 17 amino acids of linear rat alpha-TGF. Forty-two % of the effusions contained immunoreactive alpha transforming growth factor (Ir-alpha-TGF) activity, including 13 of 34 (38%) breast cancer, 12 of 24 (50%) lung cancer, and 13 of 31 (42%) ovarian cancer specimens. Concentrations ranged from 1.56 to 50 ng/ml. Only 3 of 17 control effusions from noncancer patients had low levels of activity, all less than 2 ng/ml. The presence of Ir-alpha-TGF activity correlated with patients' performance status (PS) and tumor burden. It was present in 18 of 67 (27%) effusions of patients with PS less than or equal to 2 and in 23 of 33 (70%) with PS 3 or 4 (P less than 0.0001). Only 2 of 43 (4%) patients with one site of metastatic disease had detectable Ir-alpha-TGF (mean, 0.23 ng/ml); 18 of 37 (48%) with two sites (mean, 5.22 ng/ml, P less than 0.0001); and 33 of 34 (97%) with greater than two sites (mean, 5.93 ng/ml, P = 0.002). It was present in a larger percentage of effusions from breast cancer patients with estrogen- and progesterone receptor-negative tumors. Univariate analysis revealed that detectable Ir-alpha-TGF activity, PS 3 or 4, and the number of sites of disease correlated with a shorter survival. Only Ir-alpha-TGF and PS 3 or 4 retained significance in a multivariate analysis. In conclusion, Ir-alpha-TGF is frequently detectable in effusions from cancer patients, it correlates with other known adverse prognostic factors, and its presence predicts for a poor survival. Further studies of alpha-TGF activity in more readily accessible body fluids such as serum or urine are warranted.
α转化生长因子（α-TGFs）是一类多肽，可刺激多种未转化细胞在体外进行不依赖贴壁的生长，并且被认为参与肿瘤细胞的自分泌刺激。多种人类癌症可分泌α-TGF活性，这使其有可能作为一种肿瘤标志物。使用针对线性大鼠α-TGF C端17个氨基酸的羊抗体，通过放射免疫测定法检测了130例患有各种癌症患者的积液中的α-TGF活性。42%的积液含有免疫反应性α转化生长因子（Ir-α-TGF）活性，包括34例乳腺癌患者中的13例（38%）、24例肺癌患者中的12例（50%）以及31例卵巢癌标本中的13例（42%）。浓度范围为1.56至50 ng/ml。17例非癌症患者的对照积液中只有3例活性水平较低，均低于2 ng/ml。Ir-α-TGF活性的存在与患者的体能状态（PS）和肿瘤负荷相关。在PS小于或等于2的患者的67例积液中有18例（27%）存在该活性，而在PS为3或4的患者的33例积液中有23例（70%）存在该活性（P<0.0001）。只有43例（4%）有一个转移病灶的患者中的2例可检测到Ir-α-TGF（平均值为0.23 ng/ml）；37例（48%）有两个转移病灶的患者中的18例（平均值为5.22 ng/ml，P<0.0001）；34例（97%）有两个以上转移病灶的患者中的33例（平均值为5.93 ng/ml，P = 0.002）。雌激素和孕激素受体阴性肿瘤的乳腺癌患者的积液中该活性的比例更高。单因素分析显示，可检测到的Ir-α-TGF活性、PS为3或4以及疾病转移病灶数量与较短的生存期相关。在多因素分析中只有Ir-α-TGF和PS为3或4仍具有统计学意义。总之，Ir-α-TGF在癌症患者的积液中经常可检测到，它与其他已知的不良预后因素相关，其存在预示着生存期较差。有必要对血清或尿液等更易获取的体液中的α-TGF活性进行进一步研究。
