Low density lipoproteins and Lovastatin modulate the organ-specific transendothelial migration of primary and metastatic human colon adenocarcinoma cell lines in vitro
Low density lipoproteins and Lovastatin modulate the organ-specific transendothelial migration of primary and metastatic human colon adenocarcinoma cell lines in vitro
复制标题
低密度脂蛋白和洛伐他汀在体外调节原发性和转移性人结肠腺癌细胞系的器官特异性跨内皮迁移
DOI：
10.1023/a:1006548902592
复制
发表时间：
1998
影响因子：
4
通讯作者：
S. Cohen
中科院分区：
文献类型：
--
作者：
N. Mehta;J. Hordines;D. Sykes;R. Doerr;S. Cohen
肿瘤细胞停滞和肿瘤迁移是肿瘤转移级联过程中的两个关键步骤。我们推测，这些步骤可能是由低密度脂蛋白(LDL)诱导的微血管内皮细胞(MVEC)激活促进的。我们研究的目的是研究富含低密度脂蛋白的环境的生物学效应，以及抗胆固醇药物洛伐他汀对肿瘤转移行为的影响。SW480和SW620是来自同一患者的原发和转移性人结肠腺癌细胞株。我们研究了低密度脂蛋白对两种肿瘤细胞系跨人脑、肺、肝和真皮内皮细胞单层的黏附和迁移的影响。用低密度脂蛋白(100 mg/ml)处理MVEC和肿瘤细胞24 h后进行黏附和迁移实验，虽然转移性SW620细胞对MVEC的黏附能力强于原代SW480细胞，但SW480和SW620细胞的低密度脂蛋白处理不影响肿瘤细胞对MVEC的黏附。相反，当MVEC用低密度脂蛋白预处理时，肿瘤细胞跨内皮单分子层的迁移显著增加。低密度脂蛋白对肿瘤细胞的跨内皮细胞迁移无明显影响。洛伐他汀是胆固醇生物合成中的限速酶HMG-CoA还原酶的抑制剂。它已被证明在体外具有抗肿瘤活性。我们研究了洛伐他汀对肿瘤细胞动力学和肿瘤细胞跨血管内皮细胞迁移的影响。观察洛伐他汀(30 mg/ml)处理前后肿瘤细胞的生长曲线和迁移能力。用洛伐他汀处理未刺激或低密度脂蛋白刺激的MVEC(100 mg/ml)24 h后，进行细胞迁移实验。洛伐他汀对转移性SW620细胞体外生长的抑制作用强于侵袭性SW480E细胞。洛伐他汀(30 mg/ml)对肿瘤细胞的跨内皮细胞迁移无明显抑制作用。最后，与未治疗的小鼠相比，给予洛伐他汀有效地抑制了Balb/c小鼠肝脏中MCA-26肿瘤集落的数量。*Lippincott Williams&Wilkins
Tumor cell arrest and tumor migration are two of the critical steps in the metastatic cascade. We hypothesized that these steps may be facilitated by the low density lipoprotein (LDL)-induced activation of microvessel endothelial cells (MVEC). The purpose of our study was to investigate the biological effects of an LDL-enriched milieu and the effects of the anticholesterol drug Lovastatin on metastatic behavior. The SW480 and SW620 are primary and metastatic human colonic adenocarcinoma cell lines derived from the same patient. We investigated the effect of LDL on adhesion and migration of the two tumor cell lines across human brain, lung, liver and dermal endothelial monolayers. Adhesion and migration assays were done before and after pretreat-ment of the MVEC or tumor cells with LDL (100 mg/ml) for 24 h. Although metastatic SW620 cells were more adherent to MVEC compared with primary SW480 cells, LDL pretreatment of SW480 and SW620 cells did not affect tumor cell adhesion to MVEC. In contrast, tumor cell migration was significantly increased across endothelial monolayers when MVEC were pretreated with LDL. Transendothelial cell migration was not sig-nificantly affected by pretreatment of the tumor cells with LDL. Lovastatin is an inhibitor of HMG-CoA reduc-tase, the rate-limiting enzyme in cholesterol biosynthesis. It has been shown to have anti-tumor activity in vitro. We investigated the effect of Lovastatin on tumor cell kinetics and tumor cell migration across MVEC. Growth curves and migration assays were done before and after pretreatment of the tumor cells with Lovastatin (30 mg/ml). Migration assays were also done after treatment of unstimulated or LDL-stimulated MVEC (100 mg/ml) for 24 h with Lovastatin. Lovastatin inhibited the in vitro growth of the metastatic SW620 cell line to a greater extent than the invasive SW480E cell line. On the other hand, pretreatment of tumor cells with Lovastatin (30 mg/ml) did not suppress transendothelial tumor cell migration of tumor cells. Finally, Lovastatin given to mice effectively suppressed the number of MCA-26 tumor colonies in the liver of Balb/c mice com-pared with untreated mice. ©Lippincott Williams & Wilkins
登录
查看更多内容
影响因子：
11.2
作者：
I. Fidler
通讯作者：
I. Fidler
胆固醇生物合成抑制剂洛伐他汀抑制 B16F10 小鼠黑色素瘤的转移。
DOI：
--
发表时间：
1993
期刊：
Invasion & metastasis
影响因子：
--
作者：
Jani,JP;Specht,S;Stemmler,N;Blanock,K;Singh,SV;Gupta,V;Katoh,A
通讯作者：
Katoh,A
小鼠肿瘤细胞与毛细血管内皮之间粘附的特异性：体内优先转移的体外相关性。
影响因子：
11.2
作者：
Auerbach,R;Lu,WC;Pardon,E;Gumkowski,F;Kaminska,G;Kaminski,M
通讯作者：
Kaminski,M
低密度脂蛋白致动脉粥样硬化水平对培养的人内皮细胞的干扰。
DOI：
--
发表时间：
1988
期刊：
The American journal of pathology
影响因子：
--
作者：
Holland,JA;Pritchard,KA;Rogers,NJ;Stemerman,MB
通讯作者：
Stemerman,MB
DOI：
10.1006/bbrc.1994.2861
发表时间：
1994-12-30
影响因子：
3.1
作者：
JONES, KD;COULDWELL, WT;LAW, RE
通讯作者：
LAW, RE