Stearoyl-CoA desaturase 1 and paracrine diffusible signals have a major role in the promotion of breast cancer cell migration induced by cancer-associated fibroblasts.
Stearoyl-CoA desaturase 1 and paracrine diffusible signals have a major role in the promotion of breast cancer cell migration induced by cancer-associated fibroblasts.
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硬脂酰-COA去饱和酶1和旁分泌可扩散信号在促进由癌症相关的成纤维细胞诱导的乳腺癌细胞迁移中起着重要作用。
DOI：
10.1038/bjc.2015.135
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发表时间：
2015-05-12
影响因子：
8.8
通讯作者：
Sica, G.
中科院分区：
文献类型：
--
作者：
Angelucci, C.;Maulucci, G.;Colabianchi, A.;Iacopino, F.;D'Alessio, A.;Maiorana, A.;Palmieri, V.;Papi, M.;De Spirito, M.;Di Leone, A.;Masetti, R.;Sica, G.
尽管基质对乳腺癌的发展和进展的贡献是公认的，但肿瘤微环境的有效靶向仍然是一个有待解决的挑战。我们以前报道过，正常成纤维细胞（NF），特别是乳腺癌相关成纤维细胞（CAFs）诱导上皮细胞向间充质细胞转化，并增加细胞膜流动性和迁移良好（MCF-7）和分化不良（MDA-MB-231）乳腺癌细胞。这项研究旨在更好地确定所发挥的作用，特别是CAFs，在促进乳腺肿瘤细胞迁移。建立成纤维细胞/乳腺癌细胞共培养体系，研究NF和CAFs对MCF-7和MDA-MB-231细胞中调节膜流动性的主要酶硬脂酰辅酶A去饱和酶1（SCD 1）基因和蛋白表达的影响，以及对其转录因子固醇调节元件结合蛋白1（SREBP 1）的蛋白水平和活性的影响。为了评估SREBP 1在调节SCD 1表达中的作用，还测定了用SREBP 1抑制剂处理的肿瘤细胞中的去饱和酶水平。通过在SCD 1抑制（通过小干扰RNA（siRNA）或siRNA）的癌细胞中的伤口愈合测定来评估迁移，并且还评估了CAF条件培养基的作用。为了确定基质来源的信号在癌细胞迁移速度中的作用，在存在肝细胞生长因子、转化生长因子-β或碱性成纤维细胞生长因子的中和抗体的情况下进行细胞追踪分析。在两种癌细胞系中，SCD 1 mRNA和蛋白质表达增加了2 - 3倍，特别是通过CAF，这两种癌细胞系似乎依赖于MCF-7中的SREBP 1活性，但在MDA-MB-231细胞中不依赖。siRNA介导的和药理学抑制的SCD 1损害肿瘤细胞迁移，也促进了由CAF释放的可溶性因子。通过中和上述生长因子，成纤维细胞触发的癌细胞迁移速度的增加显著降低或消除。这些结果为理解CAFs在促进肿瘤细胞迁移中的作用提供了进一步的见解，这可能有助于设计新的基于基质的治疗策略。
Despite the recognised contribution of the stroma to breast cancer development and progression, the effective targeting of the tumor microenvironment remains a challenge to be addressed. We previously reported that normal fibroblasts (NFs) and, notably, breast cancer-associated fibroblasts (CAFs) induced epithelial-to-mesenchymal transition and increases in cell membrane fluidity and migration in well- (MCF-7) and poorly-differentiated (MDA-MB-231) breast cancer cells. This study was designed to better define the role played, especially by CAFs, in promoting breast tumor cell migration. Fibroblast/breast cancer cell co-cultures were set up to investigate the influence of NFs and CAFs on gene and protein expression of Stearoyl-CoA desaturase 1 (SCD1), the main enzyme regulating membrane fluidity, as well as on the protein level and activity of its transcription factor, the sterol regulatory element-binding protein 1 (SREBP1), in MCF-7 and MDA-MB-231 cells. To assess the role of SREBP1 in the regulation of SCD1 expression, the desaturase levels were also determined in tumor cells treated with an SREBP1 inhibitor. Migration was evaluated by wound-healing assay in SCD1-inhibited (by small-interfering RNA (siRNA) or pharmacologically) cancer cells and the effect of CAF-conditioned medium was also assessed. To define the role of stroma-derived signals in cancer cell migration speed, cell-tracking analysis was performed in the presence of neutralising antibodies to hepatocyte growth factor, transforming growth factor-β or basic fibroblast growth factor. A two to three fold increase in SCD1 mRNA and protein expression has been induced, particularly by CAFs, in the two cancer cell lines that appear to be dependent on SREBP1 activity in MCF-7 but not in MDA-MB-231 cells. Both siRNA-mediated and pharmacological inhibition of SCD1 impaired tumor cells migration, also when promoted by CAF-released soluble factors. Fibroblast-triggered increase in cancer cell migration speed was markedly reduced or abolished by neutralising the above growth factors. These results provide further insights in understanding the role of CAFs in promoting tumor cell migration, which may help to design new stroma-based therapeutic strategies.
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影响因子：
5.2
作者：
Igal RA
通讯作者：
Igal RA
DOI：
10.1073/pnas.0401064101
发表时间：
2004-04-06
影响因子：
11.1
作者：
Kuperwasser, C;Chavarria, T;Weinberg, RA
通讯作者：
Weinberg, RA
影响因子：
50.3
作者：
Neve, Richard M.;Chin, Koei;Gray, Joe W.
通讯作者：
Gray, Joe W.
影响因子：
3.7
作者：
Cao XC;Zhang WR;Cao WF;Liu BW;Zhang F;Zhao HM;Meng R;Zhang L;Niu RF;Hao XS;Zhang B
通讯作者：
Zhang B
影响因子：
1.9
作者：
Ntambi, JM;Miyazaki, A;Dobrzyn, A
通讯作者：
Dobrzyn, A