Intra-tumor L-methionine level highly correlates with tumor size in both pancreatic cancer and melanoma patient-derived orthotopic xenograft (PDOX) nude-mouse models.
Intra-tumor L-methionine level highly correlates with tumor size in both pancreatic cancer and melanoma patient-derived orthotopic xenograft (PDOX) nude-mouse models.
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DOI：
10.18632/oncotarget.24264
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发表时间：
2018-02-16
期刊：
影响因子：
--
通讯作者：
Hoffman RM
中科院分区：
文献类型：
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作者：
Kawaguchi K;Han Q;Li S;Tan Y;Igarashi K;Miyake K;Kiyuna T;Miyake M;Chemielwski B;Nelson SD;Russell TA;Dry SM;Li Y;Singh AS;Eckardt MA;Unno M;Eilber FC;Hoffman RM
生长对甲硫氨酸（MET）的过度需求，称为MET依赖性，似乎是癌症中的一般代谢缺陷。我们以前已经表明，癌细胞的生长可以选择性地阻止MET限制，如重组蛋氨酸酶（rMET酶）。在本研究中，我们利用患者来源的胰腺癌或黑色素瘤原位异种移植（PDOX）裸鼠模型来确定肿瘤内MET水平与肿瘤大小之间的关系。在肿瘤生长至100 mm3后，将PDOX裸鼠分成两组：未处理的对照组和用rMET酶（100单位，i.p.，连续14天）。在治疗开始后第14天，测量肿瘤内MET水平，发现其与肿瘤体积高度相关，在胰腺癌PDOX（p<0.0001，R2=0.89016）和黑素瘤PDOX（p<0.0001，R2=0.88114）中均如此。低浓度MET组肿瘤较小。目前的结果表明，患者肿瘤的生长高度依赖于MET，并且rMET酶有效地降低了肿瘤MET。
An excessive requirement for methionine (MET) for growth, termed MET dependence, appears to be a general metabolic defect in cancer. We have previously shown that cancer-cell growth can be selectively arrested by MET restriction such as with recombinant methioninase (rMETase). In the present study, we utilized patient-derived orthotopic xenograft (PDOX) nude mouse models with pancreatic cancer or melanoma to determine the relationship between intra-tumor MET level and tumor size. After the tumors grew to 100 mm3, the PDOX nude mice were divided into two groups: untreated control and treated with rMETase (100 units, i.p., 14 consecutive days). On day 14 from initiation of treatment, intra-tumor MET levels were measured and found to highly correlate with tumor volume, both in the pancreatic cancer PDOX (p<0.0001, R2=0.89016) and melanoma PDOX (p<0.0001, R2=0.88114). Tumors with low concentration of MET were smaller. The present results demonstrates that patient tumors are highly dependent on MET for growth and that rMETase effectively lowers tumor MET.