Metabolic interaction between cancer cells and stromal cells according to breast cancer molecular subtype.
Metabolic interaction between cancer cells and stromal cells according to breast cancer molecular subtype.
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DOI：
10.1186/bcr3472
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Koo JS
中科院分区：
文献类型：
--
作者：
Choi J;Kim DH;Jung WH;Koo JS
本研究的目的是研究乳腺癌不同分子亚型中代谢、线粒体和自噬状态相关标志物的差异表达。使用从740例乳腺癌中产生的组织微阵列切片，我们对Glut-1、CAIX、MCT 4、ATP合酶、转氨酶、BNIP 3、Beclin-1、LC 3A、LC 3B和p62进行免疫组织化学染色。根据雌激素受体（ER）、孕激素（PR）、HER 2的免疫组化表达和Ki-67标记指数，将病例分为管腔型A、管腔型B、HER 2和三阴性乳腺癌（TNBC）。我们通过评估Glut-1和CAIX表达，根据糖酵解状态进一步将肿瘤的代谢表型分类如下：瓦尔堡型：肿瘤（糖酵解型），基质（非糖酵解型）;反向瓦尔堡型：肿瘤（非糖酵解型），基质（糖酵解型）;混合型：肿瘤（糖酵解型），基质（糖酵解型）;和无效型：肿瘤（非糖酵解型），基质（非糖酵解型）。Glut-1、MCT 4和LC 3A在TNBC中的表达最高，而在管腔A型中的表达最低（P < 0.001）。其中瓦尔堡型298例（40.3%），反瓦尔堡型54例（7.3%），混合型62例（8.4%），无效型326例（44.0%）。混合型的组织学分级、ER、PR阳性率及Ki-67指数均高于非混合型（P < 0.001）。TNBC以瓦尔堡型和混合型为主，管腔A型以反向瓦尔堡型和无效型为主（P < 0.001）。乳腺癌在其代谢状态上是异质性的，因此它可以被分类为各种代谢表型。具体而言，瓦尔堡和混合型与TNBC具有强关联，而反向瓦尔堡和无效型与管腔型具有关联，表明代谢表型与乳腺癌生物学之间的相关性。
The aim of this study was to investigate the differential expression of markers related to metabolic, mitochondrial and autophagy status in different molecular subtypes of breast cancer. Using tissue microarray sections generated from 740 cases of breast cancer, we performed immunohistochemical staining for Glut-1, CAIX, MCT4, ATP synthase, glutaminase, BNIP3, Beclin-1, LC3A, LC3B and p62. Based on the immunohistochemical expression of estrogen receptor (ER), progesterone (PR), HER2, and Ki-67 labeling index, the cases were classified into luminal A, luminal B, HER2 and triple-negative breast cancer (TNBC). We further classified metabolic phenotypes of tumors according to glycolytic status by assessing Glut-1 and CAIX expression as follows: Warburg type: tumor (glycolysis type), stroma (nonglycolysis type); reverse Warburg type: tumor (nonglycolysis type), stroma (glycolysis type); mixed type: tumor (glycolysis type), stroma (glycolysis type); and null type: tumor (nonglycolysis type), stroma (nonglycolysis type). Expression of Glut-1, MCT4 and LC3A was highest in TNBC and lowest in luminal A type (P < 0.001). Tumors were classified into 298 Warburg type (40.3%), 54 reverse Warburg type (7.3%), 62 mixed type (8.4%) and 326 null type (44.0%). The mixed type had a higher histologic grade, ER negativity, PR negativity and Ki-67 index, whereas the null type showed lower histologic grade, ER positivity, PR positivity and Ki-67 index (P < 0.001). TNBC constituted the major portion of Warburg and mixed types, and luminal A consisted mainly of reverse Warburg and null types (P < 0.001). Breast cancer is heterogeneous in its metabolic status, and therefore it can be classified into various metabolic phenotypes. Specifically, the Warburg and mixed types had strong associations with TNBC, whereas reverse the Warburg and null types had associations with the luminal type, suggesting a correlation between metabolic phenotype and the biology of breast cancer.
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影响因子：
4.3
作者：
Martinez-Outschoorn, Ubaldo E.;Pavlides, Stephanos;Sotgia, Federica
通讯作者：
Sotgia, Federica
影响因子：
4.3
作者：
Bonuccelli, Gloria;Tsirigos, Aristotelis;Lisanti, Michael P.
通讯作者：
Lisanti, Michael P.
影响因子：
4.3
作者：
Martinez-Outschoorn, Ubaldo E.;Trimmer, Casey;Sotgia, Federica
通讯作者：
Sotgia, Federica
影响因子：
3
作者：
Park, So Yeon;Kim, Ku Sang;Kim, Sung-Won
通讯作者：
Kim, Sung-Won
影响因子：
5
作者：
Camp, RL;Charette, LA;Rimm, DL
通讯作者：
Rimm, DL