Effects of AGM-1470 and pentosan polysulphate on tumorigenicity and metastasis of FGF-transfected MCF-7 cells.
Effects of AGM-1470 and pentosan polysulphate on tumorigenicity and metastasis of FGF-transfected MCF-7 cells.
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DOI：
10.1038/bjc.1996.204
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发表时间：
1996-05
影响因子：
8.8
通讯作者：
Kern, FG
中科院分区：
文献类型：
--
作者：
McLeskey, SW;Zhang, L;Trock, BJ;Kharbanda, S;Liu, Y;Gottardis, MM;Lippman, ME;Kern, FG
先前，我们描述了FGF-1或FGF-4转染的MCF-7乳腺癌细胞，其在未治疗或他莫昔芬治疗的卵巢切除裸鼠中是致瘤性和转移性的。在这项研究中，我们评估了AGM-1470，一种抗血管生成剂，和戊聚糖多硫酸酯（PPS），一种消除FGF影响的药物，对这些FGF转染的MCF-7细胞产生的肿瘤生长和转移的影响。给未治疗或他莫昔芬治疗的卵巢切除小鼠注射FGF转染的细胞，用AGM-1470或PPS治疗，并分析肿瘤生长和转移。还在体外测定了FGF转染的MCF-7细胞和亲本MCF-7细胞对AGM-1470或PPS的敏感性。AGM-1470和PPS都抑制了注射FGF-或FGF-4转染的MCF-7细胞的未处理或他莫昔芬处理的小鼠的肿瘤生长。这种作用在他莫昔芬治疗的动物中更可靠。AGM-1470抑制亲本MCF-7或FGF转染的MCF-7细胞的贴壁依赖性生长的效力比抑制人脐静脉内皮细胞生长的效力低约10（5）倍。PPS不影响转染子或亲本细胞的体外生长。因此，对肿瘤的生长抑制作用超过任一药物对组织培养中相同细胞的作用，这意味着基质成分是这些药物作用的重要决定因素。肿瘤大小与近端淋巴结转移程度呈正相关。然而，这两种药物对近端或远端淋巴结或肺转移的程度都没有显著影响。AGM-1470或PPS可能有助于乳腺癌的病例，其中血管生成是由于肿瘤细胞表达FGF，并且当与他莫昔芬组合时可能更有效。
Previously, we described FGF-1- or FGF-4-transfected MCF-7 breast carcinoma cells which are tumorigenic and metastatic in untreated or tamoxifen-treated ovariectomised nude mice. In this study, we have assessed the effects of AGM-1470, an antiangiogenic agent, and pentosan polysulphate (PPS), an agent that abrogates the effects of FGFs, on tumour growth and metastasis produced by these FGF-transfected MCF-7 cells. Untreated or tamoxifen-treated ovariectomised mice were injected with FGF-transfected cells, treated with AGM-1470 or PPS, and tumour growth and metastasis analysed. The sensitivity of FGF-transfected and parental MCF-7 cells to AGM-1470 or PPS was also determined in vitro. Both AGM-1470 and PPS inhibited tumour growth in otherwise untreated or tamoxifen-treated mice injected with either FGF- or FGF-4-transfected MCF-7 cells. This effect was more reliably seen in tamoxifen-treated animals. AGM-1470 was about 10(5) times less potent in inhibiting the anchorage-dependent growth of parental MCF-7 or FGF-transfected MCF-7 cells than in inhibiting the growth of human umbilical vein endothelial cells. PPS did not affect the in vitro growth of the transfectants or parental cells. Thus, the growth-inhibitory effect on tumours was in excess of the effect of either drug on the same cells in tissue culture, implying that stromal elements are important determinants of the effects of these drugs. There was a positive correlation between tumour size and the extent of proximal lymph node metastasis. However, neither drug had a significant effect on the extent of metastasis to proximal or distal lymph nodes or lungs. AGM-1470 or PPS may be helpful in cases of breast carcinoma in which angiogenesis is due to expression of FGFs by the tumour cells and may be more effective when combined with tamoxifen.
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DOI：
10.1097/00000421-199112002-00005
发表时间：
1991-01-01
影响因子：
2.6
作者：
KNABBE, C;ZUGMAIER, G;DICKSON, RB
通讯作者：
DICKSON, RB
影响因子：
5.6
作者：
GAJDUSEK, CM;LUO, ZG;MAYBERG, MR
通讯作者：
MAYBERG, MR
影响因子：
64.8
作者：
FOLKMAN, J;WATSON, K;HANAHAN, D
通讯作者：
HANAHAN, D
影响因子：
2.4
作者：
BREM, H;GRESSER, I;FOLKMAN, J
通讯作者：
FOLKMAN, J
影响因子：
5.6
作者：
BELFORD, DA;HENDRY, IA;PARISH, CR
通讯作者：
PARISH, CR