TRANSFORMING GROWTH FACTOR-BETA-1 OVERPRODUCTION IN PROSTATE-CANCER - EFFECTS ON GROWTH-INVIVO AND INVITRO
TRANSFORMING GROWTH FACTOR-BETA-1 OVERPRODUCTION IN PROSTATE-CANCER - EFFECTS ON GROWTH-INVIVO AND INVITRO
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DOI：
10.1210/me.6.1.15
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发表时间：
1992-01-01
影响因子：
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通讯作者：
BARRACK, ER
中科院分区：
文献类型：
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作者：
STEINER, MS;BARRACK, ER
我们以前发现，转化生长因子-β-1（TGF-β-1）mRNA水平显着升高，在大鼠前列腺癌（Dunning R3327亚系）相比，在正常前列腺的水平。我们的目标是确定TGF-β 1的表达升高是否与体内前列腺癌的生长具有生物学相关性。我们选择R3327-MATLyLu前列腺癌上皮细胞系作为我们的模型，该细胞系在体内重新接种时产生转移性间变性肿瘤。我们的方法是用编码潜伏性TGF-β-1的表达载体稳定转染MATLyLu细胞，并分离过表达TGF-β-1 mRNA的细胞亚克隆。我们还分离了用缺乏TGF-β-1 mRNA的对照载体转染的MATLyLu细胞的亚克隆。我们还分离了用缺乏TGF-β-1 cDNA插入片段的对照载体转染的MATLyLu细胞的亚克隆。然后，我们研究了这些细胞在体内和体外的生长。在体内皮下接种10（6）个细胞后20天，与对照MATLyLu肿瘤（肺转移，21%;淋巴结转移，7%）相比，TGF-β-1过量产生的MATLyLu肿瘤大50%，坏死明显较少，并且产生更广泛的转移性疾病（所有肺叶中73%的肺转移和88%的动物的淋巴结转移）。因此，体内产生的TGF-β-1具有生物活性，可能通过对宿主和/或肿瘤细胞本身的作用，可以促进前列腺癌的生长、生存力和侵袭性。当在体外跟踪时，TGF-β-1过度产生的细胞生长受到抑制，但这种效应是短暂的，因为细胞随后恢复增殖。生长抑制是由于TGF-β，因为它可以通过TGF-β中和抗体来预防。因此，前列腺癌细胞可以激活并响应分泌的潜伏性TGF-β-1，尽管细胞在体外被短暂抑制，但没有生长的净抑制。细胞对内源性产生的TGF-β-1应答的能力表明，TGF-β-1过表达至少部分地通过TGF-β-1对肿瘤细胞本身的作用而增强体内肿瘤生长。
We found previously that transforming growth factor-beta-1 (TGF-beta-1) mRNA levels are markedly elevated in rat prostate cancer (Dunning R3327 sublines) compared to levels in normal prostate. Our goal was to determine whether elevated expression of TGF-beta-1 is biologically relevant to prostate cancer growth in vivo. We chose as our model the R3327-MATLyLu prostate cancer epithelial cell line, which produces metastatic anaplastic tumors when reinoculated in vivo. Our approach was to stably transfect MATLyLu cells with an expression vector that codes for latent TGF-beta-1 and to isolate subclones of cells that over-expressed TGF-beta-1 mRNA. We also isolated a subclone of MATLyLu cells transfected with a control vector lacking the TGF-beta-1 mRNA. We also isolated a subclone of MATLyLu cells transfected with a control vector lacking the TGF-beta-1 cDNA insert. We then studied the growth of these cells in vivo and in vitro. Twenty days after sc inoculation of 10(6) cells in vivo, TGF-beta-1-overproducing MATLyLu tumors were 50% larger, markedly less necrotic, and produced more extensive metastatic disease (lung metastases in 73% of all lobes and lymph node metastases in 88% of animals) compared to control MATLyLu tumors (lung metastases, 21%; lymph node metastases, 7%). Thus, TGF-beta-1 produced in vivo is biologically active and can promote prostate cancer growth, viability, and aggressiveness, perhaps via effects on the host and/or on the tumor cells themselves. When followed in vitro, TGF-beta-1-overproducing cells became growth inhibited, but this effect was transient as cells subsequently resumed proliferating. Growth inhibition was due to TGF-beta, because it could be prevented by TGF-beta-neutralizing antibody. Therefore, prostate cancer cells can activate and respond to secreted latent TGF-beta-1, and although the cells are transiently inhibited in vitro, there is no net inhibition of growth. The ability of the cells to respond to endogenously produced TGF-beta-1 suggests that TGF-beta-1 overexpression enhances tumor growth in vivo at least in part via an effect of TGF-beta-1 on the tumor cells themselves.