B-cell precursor acute lymphoblastic leukemia and stromal cells communicate through Galectin-3.
B-cell precursor acute lymphoblastic leukemia and stromal cells communicate through Galectin-3.
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DOI：
10.18632/oncotarget.3409
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发表时间：
2015-05-10
期刊：
影响因子：
--
通讯作者：
Heisterkamp N
中科院分区：
文献类型：
--
作者：
Fei F;Joo EJ;Tarighat SS;Schiffer I;Paz H;Fabbri M;Abdel-Azim H;Groffen J;Heisterkamp N
b细胞前体急性淋巴细胞白血病（pre-B ALL）细胞和骨髓基质细胞之间的分子相互作用提供微环境介导的抗治疗药物保护，目前还不明确。半乳糖凝集素-3 （Lgals3）是一种多功能的半乳糖结合凝集素，据报道存在于不同细胞类型的细胞核、细胞质和细胞外空间。我们之前报道过与基质共培养的ALL细胞含有高水平的半乳糖凝集素-3。我们在这里证实，与更成熟的b系癌症相比，在ALL细胞内和细胞上检测到的半乳糖凝集素-3来源于基质细胞，基质细胞在其表面表达半乳糖凝集素-3，并将其作为可溶性蛋白分泌到外泌体中。可溶性和基质结合的半乳糖凝集素-3被ALL细胞内化，运输到细胞核并刺激内源性LGALS3 mRNA的转录。当人和小鼠ALL细胞在与保护性基质细胞接触时对不同药物产生耐受性时，半乳糖凝集素-3蛋白水平持续升高。这与ALL细胞中半乳糖凝集素-3转录的诱导有关。因此，来自基质的半乳糖凝集素-3在药物治疗持续应激的前b ALL细胞中被内源性半乳糖凝集素-3补充。我们的数据表明间质Galectin-3可能通过自身诱导Galectin-3 mRNA和补救性nf - κ b通路激活来保护ALL细胞。由于内源性合成的半乳糖凝集素-3可以保护b前ALL细胞免受药物治疗，因此我们确定半乳糖凝集素-3可能是抵消基质保护作用的一个靶点。
The molecular interactions between B-cell precursor acute lymphoblastic leukemia (pre-B ALL) cells and stromal cells in the bone marrow that provide microenvironmentally-mediated protection against therapeutic drugs are not well-defined. Galectin-3 (Lgals3) is a multifunctional galactose-binding lectin with reported location in the nucleus, cytoplasm and extracellular space in different cell types. We previously reported that ALL cells co-cultured with stroma contain high levels of Galectin-3. We here establish that, in contrast to more mature B-lineage cancers, Galectin-3 detected in and on the ALL cells originates from stromal cells, which express it on their surface, secrete it as soluble protein and also in exosomes. Soluble and stromal-bound Galectin-3 is internalized by ALL cells, transported to the nucleus and stimulates transcription of endogenous LGALS3 mRNA. When human and mouse ALL cells develop tolerance to different drugs while in contact with protective stromal cells, Galectin-3 protein levels are consistently increased. This correlates with induction of Galectin-3 transcription in the ALL cells. Thus Galectin-3 sourced from stroma becomes supplemented by endogenous Galectin-3 production in the pre-B ALL cells that are under continuous stress from drug treatment. Our data suggest that stromal Galectin-3 may protect ALL cells through auto-induction of Galectin-3 mRNA and tonic NFκB pathway activation. Since endogenously synthesized Galectin-3 protects pre-B ALL cells against drug treatment, we identify Galectin-3 as one possible target to counteract the protective effects of stroma.
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影响因子：
7.2
作者：
Feldhahn N;Arutyunyan A;Stoddart S;Zhang B;Schmidhuber S;Yi SJ;Kim YM;Groffen J;Heisterkamp N
通讯作者：
Heisterkamp N
影响因子：
3
作者：
Haudek, Kevin C.;Spronk, Kimberly J.;Voss, Patricia G.;Patterson, Ronald J.;Wang, John L.;Arnoys, Eric J.
通讯作者：
Arnoys, Eric J.
DOI：
10.1073/pnas.0903497106
发表时间：
2009-08-25
影响因子：
11.1
作者：
Chen, Huan-Yuan;Fermin, Agnes;Liu, Fu-Tong
通讯作者：
Liu, Fu-Tong
影响因子：
4.2
作者：
Fredly, Hanne;Ersvaer, Elisabeth;Bruserud, Oystein
通讯作者：
Bruserud, Oystein
影响因子：
5.7
作者：
Fei F;Stoddart S;Groffen J;Heisterkamp N
通讯作者：
Heisterkamp N