Macdonald Erin B, Begovatz Paul, Barton Gregory P, Erickson-Bhatt Sarah, Inman David R, Cox Benjamin L, Eliceiri Kevin W, Strigel Roberta M, Ponik Suzanne M, Fain Sean B
Department of Medical Physics, University of Wisconsin-Madison, 1111 Highland Ave., Madison, WI 53705, USA.
Morgridge Institute for Research, 330 N. Orchard St., Madison, WI 53715, USA.
Metabolites. 2021 Apr 27;11(5):274. doi: 10.3390/metabo11050274.
This study uses dynamic hyperpolarized [1-C]pyruvate magnetic resonance spectroscopic imaging (MRSI) to estimate differences in glycolytic metabolism between highly metastatic (4T1, = 7) and metastatically dormant (4T07, = 7) murine breast cancer models. The apparent conversion rate of pyruvate-to-lactate (k) and lactate-to-pyruvate area-under-the-curve ratio (AUC) were estimated from the metabolite images and compared with biochemical metabolic measures and immunohistochemistry (IHC). A non-significant trend of increasing k ( = 0.17) and AUC ( = 0.11) from 4T07 to 4T1 tumors was observed. No significant differences in tumor IHC lactate dehydrogenase-A (LDHA), monocarboxylate transporter-1 (MCT1), cluster of differentiation 31 (CD31), and hypoxia inducible factor-α (HIF-1α), tumor lactate-dehydrogenase (LDH) activity, or blood lactate or glucose levels were found between the two tumor lines. However, AUC was significantly correlated with tumor LDH activity ( = 0.621, = 0.027) and blood glucose levels ( = -0.474, = 0.042). k displayed a similar, non-significant trend for LDH activity ( = 0.480, = 0.114) and blood glucose levels ( = -0.414, = 0.088). Neither k nor AUC were significantly correlated with blood lactate levels or tumor LDHA or MCT1. The significant positive correlation between AUC and tumor LDH activity indicates the potential of AUC as a biomarker of glycolytic metabolism in breast cancer models. However, the lack of a significant difference between in vivo tumor metabolism for the two models suggest similar pyruvate-to-lactate conversion despite differing metastatic potential.
本研究使用动态超极化[1-C]丙酮酸磁共振波谱成像（MRSI）来评估高转移性（4T1，n = 7）和转移休眠性（4T07，n = 7）小鼠乳腺癌模型之间糖酵解代谢的差异。从代谢物图像中估计丙酮酸向乳酸的表观转化率（k）和乳酸与丙酮酸的曲线下面积比（AUC），并与生化代谢指标和免疫组织化学（IHC）进行比较。观察到从4T07肿瘤到4T1肿瘤，k（p = 0.17）和AUC（p = 0.11）有增加的非显著趋势。在两种肿瘤系之间，未发现肿瘤IHC乳酸脱氢酶-A（LDHA）、单羧酸转运体-1（MCT1）、分化簇31（CD31）和缺氧诱导因子-α（HIF-1α）、肿瘤乳酸脱氢酶（LDH）活性、或血乳酸或血糖水平有显著差异。然而，AUC与肿瘤LDH活性（r = 0.621，p = 0.027）和血糖水平（r = -0.474，p = 0.042）显著相关。k在LDH活性（r = 0.480，p = 0.114）和血糖水平（r = -0.414，p = 0.088）方面显示出类似的非显著趋势。k和AUC均与血乳酸水平或肿瘤LDHA或MCT1无显著相关性。AUC与肿瘤LDH活性之间的显著正相关表明AUC作为乳腺癌模型中糖酵解代谢生物标志物的潜力。然而，两种模型的体内肿瘤代谢缺乏显著差异，表明尽管转移潜力不同，但丙酮酸向乳酸的转化相似。
