KISS1 over-expression suppresses metastasis of pancreatic adenocarcinoma in a xenograft mouse model.
KISS1 over-expression suppresses metastasis of pancreatic adenocarcinoma in a xenograft mouse model.
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DOI：
10.1007/s10585-010-9349-5
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发表时间：
2010-12
影响因子：
4
通讯作者：
Buchsbaum, Donald J.
中科院分区：
文献类型：
--
作者：
McNally, Lacey R.;Welch, Danny R.;Beck, Benjamin H.;Stafford, Lewis J.;Long, Joshua W.;Sellers, Jeffery C.;Huang, Zhi Q.;Grizzle, William E.;Stockard, Cecil R.;Nash, Kevin T.;Buchsbaum, Donald J.
由于在诊断这种致命疾病之前的高频率传播，确定用于治疗胰腺癌转移的分子靶点是至关重要的。由于KISS 1转移抑制因子在晚期胰腺癌中表达水平降低，我们假设KISS 1的重新表达将减少转移。表达荧光素酶的高转移性S2 VP 10细胞（S2 VP 10 L）用FLAG标记版本的KISS 1（KFM）、KFMΔSS（缺失分泌信号序列）或pcDNA 3对照质粒（CP）转染，并通过RTQ-PCR确认表达。将S2 VP 10 L细胞或转染子原位植入SCID小鼠，并使用生物发光成像监测肿瘤生长和转移。具有S2 VP 10 L-KISS 1肿瘤的小鼠比S2 VP 10 L发生更少的肝（98%）和肺（99%）转移。出乎意料的是，具有S2 VP 10 L-KFM ΔSS肿瘤的小鼠也具有减少的肝和肺转移，但具有比具有S2 VP 10 L-KISS的小鼠更多的转移。通过免疫组织化学方法，在表达KFMΔSS和KISS 1的原位肿瘤的细胞质中发现了KISS 1蛋白。在S2 VP 10 L-KISS 1肿瘤小鼠的肺中未发现转移;而KFMΔSS肺切片具有集中的KISS 1染色区域，表明KISS 1的分泌是显著减少转移所必需的。这些数据表明诱导KISS 1表达具有作为胰腺癌辅助治疗的潜力。
Identifying molecular targets for treatment of pancreatic cancer metastasis is critical due to the high frequency of dissemination prior to diagnosis of this lethal disease. Because the KISS1 metastasis suppressor is expressed at reduced levels in advanced pancreatic cancer, we hypothesized that re-expression of KISS1 would reduce metastases. Highly metastatic S2VP10 cells expressing luciferase (S2VP10L) were transfected with a FLAG-tagged version of KISS1 (KFM), KFMΔSS (with deleted secretion signal sequence), or pcDNA3 control plasmid (CP) and expression was confirmed by RTQ-PCR. SCID mice were implanted orthotopically with S2VP10L cells or transfectants and tumor growth and metastases were monitored using bioluminescence imaging. Mice with S2VP10L-KISS1 tumors developed fewer liver (98%) and lung (99%) metastases than S2VP10L. Unexpectedly, mice with S2VP10L-KFMΔSS tumors also had reduced liver and lung metastases, but had more metastases than mice with S2VP10L-KISS. KISS1 protein was found in the cytoplasm of both KFMΔSS and KISS1-expressing orthotopic tumors by immunohistochemistry. Metastases were not found in lungs of mice with S2VP10L-KISS1 tumors; whereas, KFMΔSS lung sections had regions of concentrated KISS1 staining, suggesting that secretion of KISS1 is needed to reduce metastasis significantly. These data suggest induction of KISS1 expression has potential as an adjuvant treatment for pancreatic cancer.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
10.3
作者：
Nash, Kevin T.;Phadke, Pushkar A.;Welch, Danny R.
通讯作者：
Welch, Danny R.
影响因子：
9.3
作者：
Prentice LM;Klausen C;Kalloger S;Köbel M;McKinney S;Santos JL;Kenney C;Mehl E;Gilks CB;Leung P;Swenerton K;Huntsman DG;Aparicio SA
通讯作者：
Aparicio SA
影响因子：
4
作者：
Jiang, Y;Berk, M;Xu, Y
通讯作者：
Xu, Y
影响因子：
10.3
作者：
Lee, JH;Miele, ME;Welch, DR
通讯作者：
Welch, DR