Ovarian tumor-initiating cells display a flexible metabolism.
Ovarian tumor-initiating cells display a flexible metabolism.
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DOI：
10.1016/j.yexcr.2014.08.028
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发表时间：
2014-10-15
影响因子：
3.7
通讯作者：
Schmelz EM
中科院分区：
文献类型：
--
作者：
Anderson AS;Roberts PC;Frisard MI;Hulver MW;Schmelz EM
卵巢癌进展期间代谢的改变允许增加大分子合成和不受限制的生长。然而，癌症干细胞或肿瘤起始细胞（能够重演原始肿瘤的小肿瘤细胞群）的代谢表型尚未得到很好的表征。在本研究中，我们比较了来自小鼠卵巢表面上皮（MOSE）细胞的干细胞富集细胞变体MOSE-LFLVv（TIC）与其亲本（MOSE-L）和良性前体（MOSE-E）细胞的代谢表型。TIC表现出葡萄糖和脂肪酸氧化的减少，伴随着乳酸分泌的增加。与MOSE-L细胞相比，TIC可以增加其糖酵解速率以克服寡霉素对ATP合酶的抑制，并且可以增加其耗氧速率以在解偶联时保持质子动力，类似于良性MOSE-E细胞。TIC在限制条件下具有增加的存活率，并且当用AICAR处理时具有增加的存活率，但表现出比MOSE-E和MOSE-L细胞更高的对二甲双胍的敏感性。总之，我们的数据表明，TIC具有独特的代谢特征，这可能使它们能够灵活地适应其微环境的特定条件。通过更好地了解其代谢表型和支持其生存的外部环境条件，可以设计治疗干预措施以扩展当前的治疗方案以根除TIC。
An altered metabolism during ovarian cancer progression allows for increased macromolecular synthesis and unrestrained growth. However, the metabolic phenotype of cancer stem or tumor-initiating cells, small tumor cell populations that are able to recapitulate the original tumor, has not been well characterized. In the present study, we compared the metabolic phenotype of the stem cell enriched cell variant, MOSE-LFFLv (TIC), derived from mouse ovarian surface epithelial (MOSE) cells, to their parental (MOSE-L) and benign precursor (MOSE-E) cells. TICs exhibit a decrease in glucose and fatty acid oxidation with a concomitant increase in lactate secretion. In contrast to MOSE-L cells, TICs can increase their rate of glycolysis to overcome the inhibition of ATP synthase by oligomycin and can increase their oxygen consumption rate to maintain proton motive force when uncoupled, similar to the benign MOSE-E cells. TICs have an increased survival rate under limiting conditions as well as an increased survival rate when treated with AICAR, but exhibit a higher sensitivity to metformin than MOSE-E and MOSE-L cells. Together, our data show that TICs have a distinct metabolic profile that may render them flexible to adapt to the specific conditions of their microenvironment. By better understanding their metabolic phenotype and external environmental conditions that support their survival, treatment interventions can be designed to extend current therapy regimens to eradicate TICs.
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影响因子：
7.4
作者：
Gerencser, Akos A.;Neilson, Andy;Choi, Sung W.;Edman, Ursula;Yadava, Nagendra;Oh, Richard J.;Ferrick, David A.;Nicholls, David G.;Brand, Martin D.
通讯作者：
Brand, Martin D.
影响因子：
11.5
作者：
Herzog, TJ
通讯作者：
Herzog, TJ
影响因子：
3.3
作者：
Cohen, Courtney A.;Shea, Amanda A.;Roberts, Paul C.
通讯作者：
Roberts, Paul C.
DOI：
10.1038/oby.2005.61
发表时间：
2005-03-01
期刊：
OBESITY RESEARCH
影响因子：
--
作者：
Heilbronn, LK;Civitarese, AE;Ravussin, E
通讯作者：
Ravussin, E
影响因子：
158.5
作者：
Calle, EE;Rodriguez, C;Thun, MJ
通讯作者：
Thun, MJ