SELECTIVE STIMULATION OF PROSTATIC-CARCINOMA CELL-PROLIFERATION BY TRANSFERRIN
SELECTIVE STIMULATION OF PROSTATIC-CARCINOMA CELL-PROLIFERATION BY TRANSFERRIN
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DOI：
10.1073/pnas.89.13.6197
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发表时间：
1992-07-01
影响因子：
11.1
通讯作者：
ZETTER, BR
中科院分区：
文献类型：
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作者：
ROSSI, MC;ZETTER, BR
侵袭性前列腺癌最常转移到骨骼系统。我们以前已经表明，培养的人前列腺癌细胞是高度响应的人骨髓中发现的生长因子。为了鉴定导致前列腺癌细胞增殖增加的因素，我们通过使用羟基磷灰石HPLC分离粗骨髓制剂。主要活性峰含有两个高分子量条带（M（r）= 80，000和69，000），分别与人转铁蛋白和血清白蛋白抗体发生交叉反应。骨髓转铁蛋白，通过使用DEAE-Affi-Gel Blue层析，抗转铁蛋白亲和层析，和羟基磷灰石HPLC纯化至表观均一性，显着刺激前列腺癌细胞增殖，而人血清白蛋白显示没有显着的生长因子活性。通过在抗转铁蛋白亲和柱上传代而耗尽转铁蛋白的骨髓制备物丧失了>90%的增殖活性。与前列腺癌细胞系观察到的反应相反，来自其他原发部位和转移到骨髓以外部位的各种人类恶性细胞系对纯化的骨髓来源转铁蛋白的反应降低。这些结果表明，人前列腺癌转移瘤在脊柱骨中的快速生长可能是由以下条件的组合引起的：（i）前列腺癌细胞引流到椎旁循环中，（ii）骨髓中高浓度的可用转铁蛋白，和（iii）前列腺癌细胞对转铁蛋白的促有丝分裂活性的敏感性增加。
Aggressive prostatic carcinomas most frequently metastasize to the skeletal system. We have previously shown that cultured human prostatic carcinoma cells are highly responsive to growth factors found in human bone marrow. To identify the factor(s) responsible for the increased prostatic carcinoma cell proliferation, we fractionated crude bone marrow preparations by using hydroxylapatite HPLC. The major activity peak contained two high molecular weight bands (M(r) = 80,000 and 69,000) that cross-reacted with antibodies to human transferrin and serum albumin, respectively. Bone marrow transferrin, purified to apparent homogeneity by using DEAE-Affi-Gel Blue chromatography, anti-transferrin affinity chromatography, and hydroxylapatite HPLC, markedly stimulated prostatic carcinoma cell proliferation, whereas human serum albumin showed no significant growth factor activity. Marrow preparations, depleted of transferrin by passage over an anti-transferrin affinity column, lost >90% of their proliferative activity. In contrast to the response observed with the prostatic carcinoma cell lines, a variety of human malignant cell lines, derived from other primary sites and metastatic to sites other than bone marrow, showed a reduced response to purified marrow-derived transferrin. These results suggest that rapid growth of human prostatic carcinoma metastases in spinal bone may result from a combination of conditions that include (i) drainage of prostatic carcinoma cells into the paravertebral circulation, (ii) high concentrations of available transferrin in bone marrow, and (iii) increased sensitivity of prostatic carcinoma cells to the mitogenic activity of transferrin.