Metabolic and morphological differences between rapidly proliferating cancerous and normal breast epithelial cells
Metabolic and morphological differences between rapidly proliferating cancerous and normal breast epithelial cells
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DOI：
10.1021/bp070301d
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发表时间：
2008-03-01
影响因子：
2.9
通讯作者：
Clark, Douglas S.
中科院分区：
文献类型：
--
作者：
Meadows, Adam L.;Kong, Becky;Clark, Douglas S.
比较了两种人乳腺上皮细胞群（MCF7 细胞（一种癌细胞系）和 48R 人乳腺上皮细胞 (48R HMEC)（一种非癌性、有限寿命细胞株））在相同生长速率下的代谢和形态学特征。两种细胞类型均被诱导在含有 C-13 标记葡萄糖的营养丰富的培养基中快速生长，并对细胞代谢物的同位素富集进行量化，以计算关键途径中的代谢通量。尽管它们的生长速度相似，但细胞表现出明显不同的代谢和形态特征。与 48R 细胞相比，MCF7 细胞的暴露表面积小 80%，每个细胞含有的蛋白质少 26%。令人惊讶的是，与癌细胞系相比，快速增殖的 48R 细胞表现出每细胞葡萄糖消耗率高出 225%，每细胞乳酸生成率高出 250%，并且每细胞谷氨酰胺消耗率几乎相同。然而，当根据暴露面积考虑通量时，观察到癌细胞具有更高的葡萄糖、乳酸和谷氨酰胺通量，这表明细胞膜单位面积具有优异的转运能力。 MCF7 细胞消耗氨基酸的速度也远高于蛋白质合成通常所需的速度，而 48R 细胞通常则不然。 MCF7 细胞中戊糖磷酸途径活性较高，并且谷氨酰胺向谷氨酸的流动的可逆性较小。与 48R 电池相比，MCF7 电池的能源效率显着更高，因为它们尺寸更小，而且对 TCA 循环的依赖更大。这些观察结果支持癌细胞代谢的进化模型，并提出了转移性乳腺癌代谢药物的靶点。
The metabolic and morphological characteristics of two human epithelial breast cell populations-MCF7 cells, a cancerous cell line, and 48R human mammary epithelial cells (48R HMECs), a noncancerous, finite lifespan cell strain-were compared at identical growth rates. Both cell types were induced to grow rapidly in nutrient-rich media containing C-13-labeled glucose, and the isotopic enrichment of cellular metabolites was quantified to calculate metabolic fluxes in key pathways. Despite their similar growth rates, the cells exhibited distinctly different metabolic and morphological profiles. MCF7 cells have an 80% smaller exposed surface area and contain 26% less protein per cell than the 48R cells. Surprisingly, rapidly proliferating 48R cells exhibited a 225% higher per-cell glucose consumption rate, a 250% higher per-cell lactate production rate, and a nearly identical per-cell glutamine consumption rate relative to the cancer cell line. However, when fluxes were considered on the basis of exposed area, the cancer cells were observed to have higher glucose, lactate, and glutamine fluxes, demonstrating superior transport capabilities per unit area of cell membrane. MCF7 cells also consumed amino acids at rates much higher than are generally required for protein synthesis, whereas 48R cells generally did not. Pentose phosphate pathway activity was higher in MCF7 cells, and the flux of glutamine to glutamate was less reversible. Energy efficiency was significantly higher in MCF7 cells, as a result of a combination of their smaller size and greater reliance on the TCA cycle than the 48R cells. These observations support evolutionary models of cancer cell metabolism and suggest targets for metabolic drugs in metastatic breast cancers.