TRANSFORMING GROWTH-FACTOR-BETA STIMULATES MAMMARY ADENOCARCINOMA CELL INVASION AND METASTATIC POTENTIAL
TRANSFORMING GROWTH-FACTOR-BETA STIMULATES MAMMARY ADENOCARCINOMA CELL INVASION AND METASTATIC POTENTIAL
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DOI：
10.1073/pnas.87.19.7678
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发表时间：
1990-10-01
影响因子：
11.1
通讯作者：
NAKAJIMA, M
中科院分区：
文献类型：
--
作者：
WELCH, DR;FABRA, A;NAKAJIMA, M
将13762NF乳腺癌细胞克隆MTLn3在含转化生长因子β1(0-5000pg/ml)的无血清培养液中预处理后，检测其实验性转移潜能，并在同基因F344大鼠体内接种2周后测定肺集落数，呈钟形剂量-反应曲线，表面肺转移数增加2-3倍。当剂量为50pg/ml时，增强效果最强。由于加入了中和抗转化生长因子-β抗体，其作用具有特异性。抗体阻断了所有水平的转化生长因子-β1的刺激活性，但当单独给予抗体时，中和了抗-转化生长因子-β。抗体对未处理的细胞无影响。转移潜能的增加似乎来自细胞渗出倾向的增加，如在膜侵袭培养系统中所测试的那样。MTLn3细胞穿透重组基底膜屏障的能力是未经处理的对照细胞的2-3.5倍，这取决于暴露于TGF-.BETA.1的时间长短。侵袭潜能的增加显然部分是由于IV型胶原酶(明胶溶解)增加了2到6倍，乙酰肝素酶活性增加了2.4倍。转化生长因子-β1处理MTLn3细胞不改变其在有血清存在时的生长速度或形态；但在无血清条件下生长受到抑制。同样，与人脐静脉内皮细胞单层或固定的重组基底膜或纤维连接蛋白基质的粘附性也没有变化。这些结果表明，转化生长因子-β1可能通过控制乳腺癌细胞打破和穿透基底膜屏障的能力来调节其转移潜能。
The experimental metastatic potential of 13762NF mammary adenocarcinoma clone MTLn3 was tested after pretreatment in serum-free medium containing transforming growth factor (TGF) .beta.1 at 0-5000 pg/ml. Lung colonies were measured 2 weeks after inoculation in syngeneic F344 rats, and a bell-shaped dose-response curve with 2- to 3-fold increase in number of surface lung metastases was seen. Maximal enhancement occurred at the 50 pg/ml dose level. The effect was specific because addition of neutralizing anti-TGF-.beta. antibody blocked the stimulatory activity at all levels of TGF-.beta.1 pretreatment, but when antibody was given alone, neutralizing anti-TGF-.beta. antibody had no effect on untreated cells. Increased metastatic potential appears to be from an increased propensity of cells to extravasate as tested in the membrane invasion culture system. MTLn3 cells penetrated reconstituted basement-membrane barriers 2- to 3.5-fold more than did untreated control cells, depending upon length of TGF-.BETA.1 exposure. Increased invasive potential is apparently due, in part, to a 2- to 6-fold increase in type IV collagenolytic (gelatinolytic) and a 2.4-fold increase in heparanase activity. TGF-.beta.1 treatment of MTLn3 cells did not alter their growth rate or morphology in the presence of serum; however, growth was inhibited in serum-free medium. Likewise, adhesion to human umbilical vein endothelial cell monolayers or to immobilized reconstituted basement membrane or fibronectin matrices was unchanged. These results suggest that TGF-.beta.1 may modulate metastatic potential of mammary tumor cells by controlling their ability to break down and penetrate basement membrane barriers.