Overexpression of fibroblast growth factor 1 in MCF-7 breast cancer cells facilitates tumor cell dissemination but does not support the development of macrometastases in the lungs or lymph nodes.
Overexpression of fibroblast growth factor 1 in MCF-7 breast cancer cells facilitates tumor cell dissemination but does not support the development of macrometastases in the lungs or lymph nodes.
复制标题
DOI：
--
复制
发表时间：
1999-10
期刊：
影响因子：
11.2
通讯作者：
Lurong Zhang;S. Kharbanda;S. Mcleskey;F. Kern
中科院分区：
文献类型：
--
作者：
Lurong Zhang;S. Kharbanda;S. Mcleskey;F. Kern
携带由转染成纤维细胞生长因子（FGF）1的LacZ标记的MCF-7人乳腺癌细胞产生的原发性肿瘤的小鼠经常出现微转移，但未观察到大转移。静脉注射FGF-1转染的肿瘤细胞不会产生肺部大转移，并且切除原发性肿瘤会导致自发性微转移的消失。因此，微转移瘤增殖的失败不是由于原发肿瘤释放的抑制因子，并且原发肿瘤的存在是维持微转移瘤所必需的。这表明微转移是由于原发性肿瘤的持续接种与转移部位的清除平衡所致。在肺和淋巴结的血管中捕获的肿瘤栓子和在肺静脉中观察到的单个肿瘤细胞暗示FGF-1过表达的MCF-7细胞在其外渗能力方面是缺陷的。与原发性肿瘤相比，肺组织中掺入溴脱氧尿苷的肿瘤细胞的频率始终较低，表明播散性肿瘤细胞无法维持高增殖率。与亲本MCF-7细胞相比，由转染细胞产生的FGF-1产生的血管生成增加以及伴随的向发育中血管的内渗速率增加可能是这些细胞产生的自发性微转移的潜在决定因素。
Mice bearing primary tumors produced by LacZ-tagged MCF-7 human breast carcinoma cells transfected with fibroblast growth factor (FGF) 1 have frequent micrometastases, but macrometastases are not observed. i.v. injection of FGF-1-transfected tumor cells produced no pulmonary macrometastases, and removal of primary tumors resulted in the disappearance of spontaneous micrometastases. Thus, failure of micrometastases to proliferate was not due to inhibitory factors released from the primary tumor, and the presence of the primary tumor is required for maintenance of the micrometastases. This indicates that the micrometastases result from continued seeding from the primary tumor balanced by clearance from the metastatic site. Tumor emboli trapped in the vessels of lungs and lymph nodes and single tumor cells observed in the pulmonary vein implied that FGF-1-overexpressing MCF-7 cells are deficient in their ability to extravasate. The frequency of tumor cells incorporating bromodeoxyuridine was consistently lower in lung tissues when compared with primary tumors, indicating that disseminated tumor cells were unable to maintain a high rate of proliferation. Increased angiogenesis resulting from FGF-1 production by the transfected cells with a concomitant increased rate of intravasation into developing blood vessels may be the underlying determinant of spontaneous micrometastasis produced by these cells when compared with parental MCF-7 cells.