Nicotine promotes tumor growth and metastasis in mouse models of lung cancer.
Nicotine promotes tumor growth and metastasis in mouse models of lung cancer.
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DOI：
10.1371/journal.pone.0007524
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发表时间：
2009-10-20
期刊：
影响因子：
3.7
通讯作者：
Chellappan S
中科院分区：
文献类型：
--
作者：
Davis R;Rizwani W;Banerjee S;Kovacs M;Haura E;Coppola D;Chellappan S
尼古丁是烟草烟雾中主要的成瘾成分。尽管一般认为尼古丁引发癌症的能力有限，但它能在多种系统中诱导细胞增殖和血管生成。这些特性可能使尼古丁促进已引发的肿瘤生长。在此我们表明，在肺癌小鼠模型中，尼古丁显著促进肿瘤的进展和转移。当通过腹腔注射或非处方透皮贴片给予尼古丁时，都观察到了这种效应。
在本研究中，将Line1小鼠腺癌细胞皮下接种到同基因的BALB/c小鼠体内。通过腹腔（i.p.）注射或透皮贴片给予尼古丁，导致接种的Line1肿瘤大小显著增加。一旦手术切除肿瘤，与溶媒处理的小鼠（19.5%）相比，尼古丁处理的小鼠肿瘤复发率（59.7%）明显更高。尼古丁还使背部接种的Line1肿瘤向肺部的转移增加了9倍。对移植肿瘤的这些研究扩展到了一个由烟草致癌物NNK诱发肿瘤的小鼠模型。通过腹腔注射NNK在A/J小鼠中诱发肺部肿瘤；每周三次给予1mg/kg尼古丁导致肺部形成的肿瘤大小和数量增加。此外，尼古丁显著降低上皮标志物E - 钙黏蛋白和β - 连环蛋白以及紧密连接蛋白ZO - 1的表达；这些肿瘤还显示α7烟碱型乙酰胆碱受体亚单位表达增加。我们认为，无论是通过烟草烟雾还是尼古丁补充剂接触尼古丁，都可能促进肿瘤生长和转移增加。
我们早期的结果表明，尼古丁能在培养的肺癌、乳腺癌和胰腺癌细胞中诱导侵袭和上皮 - 间质转化（EMT）。这项研究首次证明，通过腹腔注射或非处方皮肤贴片给予尼古丁，能够促进免疫健全小鼠的肿瘤生长和转移。这些结果表明，虽然尼古丁引发肿瘤形成的能力有限，但它能促进由烟草致癌物预先引发的肿瘤的进展和转移。
Nicotine is the major addictive component of tobacco smoke. Although nicotine is generally thought to have limited ability to initiate cancer, it can induce cell proliferation and angiogenesis in a variety of systems. These properties might enable nicotine to facilitate the growth of tumors already initiated. Here we show that nicotine significantly promotes the progression and metastasis of tumors in mouse models of lung cancer. This effect was observed when nicotine was administered through intraperitoneal injections, or through over-the-counter transdermal patches. In the present study, Line1 mouse adenocarcinoma cells were implanted subcutaneously into syngenic BALB/c mice. Nicotine administration either by intraperitoneal (i.p.) injection or transdermal patches caused a remarkable increase in the size of implanted Line1 tumors. Once the tumors were surgically removed, nicotine treated mice had a markedly higher tumor recurrence (59.7%) as compared to the vehicle treated mice (19.5%). Nicotine also increased metastasis of dorsally implanted Line1 tumors to the lungs by 9 folds. These studies on transplanted tumors were extended to a mouse model where the tumors were induced by the tobacco carcinogen, NNK. Lung tumors were initiated in A/J mice by i.p. injection of NNK; administration of 1 mg/kg nicotine three times a week led to an increase in the size and the number of tumors formed in the lungs. In addition, nicotine significantly reduced the expression of epithelial markers, E-Cadherin and β-Catenin as well as the tight junction protein ZO-1; these tumors also showed an increased expression of the α7 nAChR subunit. We believe that exposure to nicotine either by tobacco smoke or nicotine supplements might facilitate increased tumor growth and metastasis. Our earlier results indicated that nicotine could induce invasion and epithelial-mesenchymal transition (EMT) in cultured lung, breast and pancreatic cancer cells. This study demonstrates for the first time that administration of nicotine either by i.p. injection or through over-the-counter dermal patches can promote tumor growth and metastasis in immunocompetent mice. These results suggest that while nicotine has only limited capacity to initiate tumor formation, it can facilitate the progression and metastasis of tumors pre-initiated by tobacco carcinogens.
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DOI：
10.1083/jcb.153.5.1049
发表时间：
2001-05-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gottardi CJ;Wong E;Gumbiner BM
通讯作者：
Gumbiner BM
影响因子：
4.8
作者：
Chen, DN;Patrick, JW
通讯作者：
Patrick, JW
影响因子：
5
作者：
Clementi, F;Fornasari, D;Gotti, C
通讯作者：
Gotti, C
影响因子：
6.4
作者：
Dasgupta, Piyali;Rizwani, Wasia;Pillai, Smitha;Kinkade, Rebecca;Kovacs, Michelle;Rastogi, Shipra;Banerjee, Sarmistha;Carless, Melanie;Kim, Esther;Coppola, Domenico;Haura, Eric;Chellappan, Srikumar
通讯作者：
Chellappan, Srikumar
影响因子：
64.8
作者：
Chanock, Stephen J.;Manolio, Teri;Collins, Francis S.
通讯作者：
Collins, Francis S.