Influence of methotrexate and cisplatin on tumor progression and survival in the VM mouse model of systemic metastatic cancer
Influence of methotrexate and cisplatin on tumor progression and survival in the VM mouse model of systemic metastatic cancer
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DOI：
10.1002/ijc.24649
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发表时间：
2010-01-01
影响因子：
6.4
通讯作者：
Seyfried, Thomas N.
中科院分区：
文献类型：
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作者：
Huysentruyt, Leanne C.;Shelton, Laura M.;Seyfried, Thomas N.
我们最近发现了一种新的肿瘤（VM-M3），它自发地出现在近交系VM小鼠的大脑中。当在脑外生长时，VM-M3肿瘤表达转移的所有主要生物学过程，包括局部侵袭、内渗、免疫系统存活、外渗和涉及肺、肝、肾、脾和脑的继发性肿瘤形成。VM-M3肿瘤还表达巨噬细胞样细胞的多种特性，类似于先前在许多人转移性癌症中描述的那些特性，这表明VM-M3模型将可用于研究大多数类型的转移性癌症，而不管组织来源如何。将表达萤火虫荧光素酶（VM-M3/Fluc）的VM-M3肿瘤细胞在免疫活性和同基因VM小鼠宿主中皮下生长。甲氨蝶呤（MTX; 25 mg/kg）和顺铂（10-15 mg/kg）的抗转移作用在腹膜内注射给药一次/周，持续3周后进行评价。生物发光成像用于测量VM-M3/Fluc生长和转移。所有（12/12）对照小鼠在皮下植入VM-M3/Fluc后21天内发生全身性癌症。尽管甲氨蝶呤不能抑制VM-M3/Fluc原发肿瘤的生长，但它使肺和肝转移减少了50%，并完全抑制了向肾、脾和脑的转移。顺铂显著降低了原发性肿瘤生长，阻断了向肺、肝、肾、脾和脑的转移，并显著增加了所有治疗动物的存活率。我们的研究结果表明，VM-M3/Fluc肿瘤对MTX和顺铂的反应与人类转移性疾病的反应相似。这些发现表明，VM-M3/Fluc肿瘤是一种可靠的临床前模型，可用于评估抗转移癌症疗法和潜在的控制途径。
We recently identified a new tumor (VM-M3), which arose spontaneously in the brain of an inbred VM mouse. When grown outside the brain, the VM-M3 tumor expresses all major biological processes of metastasis to include local invasion, intravasation, immune system survival, extravasation, and secondary tumor formation involving lung, liver, kidney, spleen and brain. The VM-M3 tumor also expresses multiple properties of macrophage-like cells similar to those described previously in numerous human metastatic cancers suggesting that the VM-M3 model will be useful for studying most types of metastatic cancer, regardless of tissue origin. VM-M3 tumor cells, expressing firefly luciferase (VM-M3/Fluc), were grown subcutaneously in the immunocompetent and syngeneic VM mouse host. The antimetastatic effects of methotrexate (MTX; 25 mg/kg) and cisplatin (10-15 mg/kg) were evaluated following i.p. injections administered once/wk for 3 weeks. Bioluminescent imaging was used to measure VM-M3/Fluc growth and metastasis. All (12/12) control mice developed systemic cancer within 21 days of subcutaneous VM-M3/Fluc implantation. Although methotrexate did not inhibit VM-M3/Fluc primary tumor growth, it reduced lung and liver metastasis by 50% and completely inhibited metastasis to kidneys, spleen and brain. Cisplatin significantly reduced primary tumor growth, blocked metastasis to lung, liver, kidneys, spleen and brain, and significantly increased survival in all treated animals. Our findings show that the response of the VM-M3/Fluc tumor to MTX and cisplatin is similar to that reported in humans with metastatic disease. These findings indicate that the VM-M3/Fluc tumor is a reliable preclinical model for evaluating antimetastatic cancer therapies and underlying control pathways.