Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy.
Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy.
复制标题
DOI：
10.1084/jem.193.6.727
复制
发表时间：
2001-03-19
期刊：
影响因子：
--
通讯作者：
Pollard JW
中科院分区：
文献类型：
--
作者：
Lin EY;Nguyen AV;Russell RG;Pollard JW
在人乳腺癌中，巨噬细胞集落刺激因子（CSF-1）及其受体（CSF-1 R）的过度表达与预后不良相关。为了确定CSF-1和乳腺癌进展之间是否存在因果关系，我们将易患乳腺癌的转基因小鼠与CSF-1基因（Csf 1 op）中含有隐性无效突变的小鼠杂交，并在野生型和无效突变小鼠中跟踪肿瘤进展。CSF-1的缺乏既不影响原发性肿瘤的发生率也不影响其生长，但延迟了其向侵袭性转移性癌的发展。在Csf 1 op/Csf 1 op和野生型肿瘤易感小鼠的乳腺上皮中CSF-1的转基因表达导致癌症晚期的加速和肺转移的显著增加。这与巨噬细胞向原发性肿瘤的浸润增强有关。这些研究表明，乳腺肿瘤的生长和恶性肿瘤的发展是独立的过程，CSF-1选择性地促进后者的过程。CSF-1可能通过调节肿瘤相关巨噬细胞的浸润和功能来促进转移潜能，因为在肿瘤部位，CSF-1 R表达仅限于巨噬细胞。我们的数据表明，针对CSF-1/CSF-1 R活性的药物可能具有重要的治疗作用。
In human breast carcinomas, overexpression of the macrophage colony–stimulating factor (CSF-1) and its receptor (CSF-1R) correlates with poor prognosis. To establish if there is a causal relationship between CSF-1 and breast cancer progression, we crossed a transgenic mouse susceptible to mammary cancer with mice containing a recessive null mutation in the CSF-1 gene (Csf1op) and followed tumor progression in wild-type and null mutant mice. The absence of CSF-1 affects neither the incidence nor the growth of the primary tumors but delayed their development to invasive, metastatic carcinomas. Transgenic expression of CSF-1 in the mammary epithelium of both Csf1op/Csf1op and wild-type tumor-prone mice led to an acceleration to the late stages of carcinoma and to a significant increase in pulmonary metastasis. This was associated with an enhanced infiltration of macrophages into the primary tumor. These studies demonstrate that the growth of mammary tumors and the development to malignancy are separate processes and that CSF-1 selectively promotes the latter process. CSF-1 may promote metastatic potential by regulating the infiltration and function of tumor-associated macrophages as, at the tumor site, CSF-1R expression was restricted to macrophages. Our data suggest that agents directed at CSF-1/CSF-1R activity could have important therapeutic effects.
登录
查看更多内容
影响因子：
4.4
作者：
KACINSKI, BM
通讯作者：
KACINSKI, BM
影响因子：
4.8
作者：
Glading, A;Chang, P;Wells, A
通讯作者：
Wells, A
影响因子：
8
作者：
Bugge, TH;Lund, LR;Degen, JL
通讯作者：
Degen, JL
影响因子：
5.6
作者：
HAMILTON, JA;STANLEY, ER;SHADDUCK, RK
通讯作者：
SHADDUCK, RK
影响因子：
5.3
作者：
GUY, CT;CARDIFF, RD;MULLER, WJ
通讯作者：
MULLER, WJ