Correlation between MMPs and their inhibitors in breast cancer tumor tissue specimens and in cell lines with different metastatic potential.
Correlation between MMPs and their inhibitors in breast cancer tumor tissue specimens and in cell lines with different metastatic potential.
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MMP及其抑制剂在乳腺癌肿瘤组织标本中的抑制剂与具有不同转移潜能的细胞系中的相关性。
DOI：
10.1186/1471-2407-9-20
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发表时间：
2009-01-14
期刊：
影响因子：
3.8
通讯作者：
Sogayar MC
中科院分区：
文献类型：
--
作者：
Figueira RC;Gomes LR;Neto JS;Silva FC;Silva ID;Sogayar MC
转移性疾病而不是原发性肿瘤本身是导致大多数实体瘤（包括乳腺癌）死亡的原因。基质金属蛋白酶（MMP）、MMP的组织抑制剂（TIMP）和具有Kazal基序的逆转诱导富含半胱氨酸蛋白（RECK）在转移过程中的作用先前已被确定。然而，在所有已发表的研究中，仅在有限数量的细胞系中分析了有限数量的MMP/MMP抑制剂。在这里，我们提出了一个更全面的方法，通过分析几种MMP（MMP-2，MMP-9和MMP-14）和MMP抑制剂（TIMP-1，TIMP-2和RECK）在不同的模型（5人乳腺癌细胞系，72原发性乳腺肿瘤和30个相邻的正常组织）的表达水平。我们采用定量RT-PCR（qRT-PCR）分析了MMP-2、MMP-9和MMP-14及其抑制剂（TIMP-1、TIMP-2和RECK）在5株具有较高侵袭性和转移潜能的人乳腺癌细胞系、72例原发性乳腺肿瘤和30例癌旁正常组织中的表达水平。此外，通过在塑料或人工ECM（Matrigel）上培养这些细胞系来分析细胞-细胞外基质元件相互作用在MMPs及其抑制剂的表达和活性的调节中的作用。结果表明，无论是在细胞系模型中还是在肿瘤组织样品中，MMPs mRNA表达水平与其抑制剂的转录表达水平均显示出正相关和统计学显著性。此外，所有MMP抑制剂的表达仅在高度侵袭性和转移性细胞系中通过细胞-基质胶接触来调节。在转录水平上的酶/抑制剂平衡显著地有利于酶，这在肿瘤中比在邻近的非肿瘤组织样品中更明显。我们的研究结果表明，MMPs及其抑制剂的表达，至少在转录水平上，可能是由共同的因素和信号通路调节。因此，对这些分子的多因素分析可以提供新的和独立的预后信息，有助于为每个患者确定更适当的治疗策略。
The metastatic disease rather than the primary tumor itself is responsible for death in most solid tumors, including breast cancer. The role of matrix metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs) and Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) in the metastatic process has previously been established. However, in all published studies only a limited number of MMPs/MMP inhibitors was analyzed in a limited number of cell lines. Here, we propose a more comprehensive approach by analyzing the expression levels of several MMPs (MMP-2, MMP-9 and MMP-14) and MMP inhibitors (TIMP-1, TIMP-2 and RECK) in different models (five human breast cancer cell lines, 72 primary breast tumors and 30 adjacent normal tissues). We analyzed the expression levels of MMP-2, MMP-9 and MMP-14 and their inhibitors (TIMP-1, TIMP-2 and RECK) by quantitative RT-PCR (qRT-PCR) in five human breast cancer cell lines presenting increased invasiveness and metastatic potential, 72 primary breast tumors and 30 adjacent normal tissues. Moreover, the role of cell-extracellular matrix elements interactions in the regulation of expression and activity of MMPs and their inhibitors was analyzed by culturing these cell lines on plastic or on artificial ECM (Matrigel). The results demonstrated that MMPs mRNA expression levels displayed a positive and statistically significant correlation with the transcriptional expression levels of their inhibitors both in the cell line models and in the tumor tissue samples. Furthermore, the expression of all MMP inhibitors was modulated by cell-Matrigel contact only in highly invasive and metastatic cell lines. The enzyme/inhibitor balance at the transcriptional level significantly favors the enzyme which is more evident in tumor than in adjacent non-tumor tissue samples. Our results suggest that the expression of MMPs and their inhibitors, at least at the transcriptional level, might be regulated by common factors and signaling pathways. Therefore, the multi-factorial analysis of these molecules could provide new and independent prognostic information contributing to the determination of more adequate therapy strategies for each patient.
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DOI：
10.1073/pnas.95.22.13221
发表时间：
1998-10-27
影响因子：
11.1
作者：
Takahashi, C;Sheng, ZQ;Noda, M
通讯作者：
Noda, M
影响因子：
19
作者：
Rhee, JS;Coussens, LM
通讯作者：
Coussens, LM
影响因子：
3.8
作者：
Haupt LM;Thompson EW;Trezise AE;Irving RE;Irving MG;Griffiths LR
通讯作者：
Griffiths LR
乳腺癌中1、2、3和9类型基质金属蛋白酶的测定。
影响因子：
8.8
作者：
Remacle, A G;Noel, A;Duggan, C;McDermott, E;O'Higgins, N;Foidart, J M;Duffy, M J
通讯作者：
Duffy, M J
DOI：
10.1111/j.1349-7006.1996.tb00266.x
发表时间：
1996-06-01
期刊：
JAPANESE JOURNAL OF CANCER RESEARCH
影响因子：
--
作者：
Iwata, H;Kobayashi, S;Okada, Y
通讯作者：
Okada, Y