Cleavage of galectin-3 by matrix metalloproteases induces angiogenesis in breast cancer.
Cleavage of galectin-3 by matrix metalloproteases induces angiogenesis in breast cancer.
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DOI：
10.1002/ijc.25254
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发表时间：
2010-12-01
影响因子：
6.4
通讯作者：
Raz, Avraham
中科院分区：
文献类型：
--
作者：
Nangia-Makker, Pratima;Wang, Yi;Raz, Tirza;Tait, Larry;Balan, Vitaly;Hogan, Victor;Raz, Avraham
半乳糖凝集素-3裂解与人乳腺癌和前列腺癌的进展有关，并且部分负责小鼠模型中的肿瘤生长、血管生成和凋亡抗性。半乳糖凝集素-3基因的功能多态性决定了其对基质金属蛋白酶（MMPs）-2/-9裂解的易感性，与亚洲和高加索妇女乳腺癌发病率的种族差异有关。我们的研究的目的是评估（i）半乳糖凝集素-3的切割是否与人乳腺癌进展期间的血管生成相关，（ii）切割的半乳糖凝集素-3在诱导血管生成中的作用和（iii）确定负责诱导血管生成反应的半乳糖凝集素-3结构域。用可切割的全长半乳糖凝集素-3或其片段化肽转染半乳糖凝集素-3缺失乳腺癌细胞BT-459。将趋化性、化学侵袭、异型聚集、上皮-内皮细胞相互作用和血管生成与不可裂解的半乳糖凝集素-3进行比较。与携带不可切割的半乳糖凝集素-3的BT-549-P64细胞相比，携带可切割的半乳糖凝集素-3的BT-549-H64细胞表现出增加的趋化性、侵袭性和与内皮细胞的相互作用，导致血管生成和3D形态发生。BT-549-H64细胞诱导迁移内皮细胞的迁移和粘着斑激酶的磷酸化增加。与用半乳糖凝集素-3肽转染的BT-549细胞共培养的内皮细胞表明氨基酸1-62和33-250刺激内皮细胞的迁移和形态发生。乳腺癌进展组织阵列中血管密度和半乳糖凝集素-3裂解的免疫组织化学分析支持体外研究结果。我们的结论是，半乳糖凝集素-3的N末端的裂解，随后在肿瘤微环境中释放，部分导致乳腺癌血管生成和进展。
Galectin-3 cleavage is related to progression of human breast and prostate cancer and is partly responsible for tumor growth, angiogenesis and apoptosis resistance in mouse models. A functional polymorphism in galectin-3 gene, determining its susceptibility to cleavage by matrix metalloproteinases (MMPs)-2/-9 is related to racial disparity in breast cancer incidence in Asian and Caucasian women. The purpose of our study is to evaluate (i) if cleavage of galectin-3 could be related to angiogenesis during the progression of human breast cancer, (ii) the role of cleaved galectin-3 in induction of angiogenesis and (iii) determination of the galectin-3 domain responsible for induction of angiogenic response. Galectin-3 null breast cancer cells BT-459 were transfected with either cleavable full-length galectin-3 or its fragmented peptides. Chemotaxis, chemoinvasion, heterotypic aggregation, epithelial-endothelial cell interactions and angiogenesis were compared to noncleavable galectin-3. BT-549-H64 cells harboring cleavable galectin-3 exhibited increased chemotaxis, invasion and interactions with endothelial cells resulting in angiogenesis and 3D morphogenesis compared to BT-549-P64 cells harboring noncleavable galectin-3. BT-549-H64 cells induced increased migration and phosphorylation of focal adhesion kinase in migrating endothelial cells. Endothelial cells cocultured with BT-549 cells transfected with galectin-3 peptides indicate that amino acids 1–62 and 33–250 stimulate migration and morphogenesis of endothelial cells. Immunohistochemical analysis of blood vessel density and galectin-3 cleavage in a breast cancer progression tissue array support the in vitro findings. We conclude that the cleavage of the N terminus of galectin-3 followed by its release in the tumor microenvironment in part leads to breast cancer angiogenesis and progression.
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影响因子：
3
作者：
Ochieng, J;Furtak, V;Lukyanov, P
通讯作者：
Lukyanov, P
DOI：
10.1083/jcb.200709019
发表时间：
2008-03-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Goetz JG;Joshi B;Lajoie P;Strugnell SS;Scudamore T;Kojic LD;Nabi IR
通讯作者：
Nabi IR
影响因子：
1.6
作者：
Galfione, M;Luo, WP;Lin, SH
通讯作者：
Lin, SH
影响因子：
3.3
作者：
Fukushi, J;Makagiansar, IT;Stallcup, WB
通讯作者：
Stallcup, WB
DOI：
10.1073/pnas.90.8.3466
发表时间：
1993-04-15
影响因子：
11.1
作者：
LOTZ, MM;ANDREWS, CW;MERCURIO, AM
通讯作者：
MERCURIO, AM