Metabolic imaging: a link between lactate dehydrogenase A, lactate, and tumor phenotype.
Metabolic imaging: a link between lactate dehydrogenase A, lactate, and tumor phenotype.
复制标题
DOI：
10.1158/1078-0432.ccr-11-0397
复制
发表时间：
2011-10-01
期刊：
影响因子：
--
通讯作者：
Koutcher JA
中科院分区：
文献类型：
--
作者：
Serganova I;Rizwan A;Ni X;Thakur SB;Vider J;Russell J;Blasberg R;Koutcher JA
我们比较了两个同基因的小鼠乳腺癌细胞系和肿瘤(67NR和4T1)的代谢特征以及LDH-A表达和乳酸产生之间的关系。这些细胞系来源于单个乳腺肿瘤，具有不同的生长和代谢表型。测量细胞中LDH-A的表达、乳酸浓度、葡萄糖利用率和氧耗，并评估这些细胞系来源的原位乳腺肿瘤中肿瘤乳酸水平(通过磁共振光谱成像(MRSI)测量)和肿瘤葡萄糖利用(通过[18F]2-脱氧-2-氟-D-葡萄糖正电子发射断层扫描([18F]FDG-PET)测量)之间的潜在关系。我们发现67NR和4T1细胞在常氧和低氧条件下LDH-A的表达有显著差异。我们还表明，小的原位4T1肿瘤比相应的67NR肿瘤产生的乳酸多10倍。小的原发4T1肿瘤的高乳酸水平与强烈的匹莫硝唑染色(一种缺氧指标)有关。在较大的67NR肿瘤中观察到较弱的低氧染色，这与67NR肿瘤增大时乳酸浓度的逐渐升高和平台相一致。乳酸盐-MRSI比[18F]FDG-PET有更大的动态范围，可能是评估原发乳腺肿瘤侵袭性和转移性的更敏感的指标。
We compared the metabolic profiles and the association between LDH-A expression and lactate production in two isogenic murine breast cancer cell lines and tumors (67NR and 4T1). These cell lines were derived from a single mammary tumor and have different growth and metabolic phenotypes. LDH-A expression, lactate concentration, glucose utilization and oxygen consumption were measured in cells, and the potential relationship between tumor lactate levels (measured by magnetic resonance spectroscopic imaging (MRSI)) and tumor glucose utilization (measured by [18F] 2-deoxy-2-fluoro-D-glucose positron emission tomography ([18F]FDG-PET)) was assessed in orthotopic breast tumors derived from these cell lines. We show a substantial difference in LDH-A expression between 67NR and 4T1 cells under normoxia and hypoxia. We also show that small orthotopic 4T1 tumors generate tenfold more lactate than corresponding 67NR tumors. The high lactate levels in small primary 4T1 tumors are associated with intense pimonidazole staining (a hypoxia indicator). Less intense hypoxia staining was observed in the larger 67NR tumors, and is consistent with the gradual increase and plateau of lactate concentration in enlarging 67NR tumors. Lactate-MRSI has a greater dynamic range than [18F]FDG-PET and may be a more sensitive measure with which to evaluate the aggressive and metastatic potential of primary breast tumors.