Depletion of Lipid Efflux Pump ABCG1 Triggers the Intracellular Accumulation of Extracellular Vesicles and Reduces Aggregation and Tumorigenesis of Metastatic Cancer Cells

被引：61

作者：

Namba, Yuri ^{[1
,2
]}

Sogawa, Chiharu ^{[1
]}

Okusha, Yuka ^{[1
]}

Kawai, Hotaka ^{[3
]}

Itagaki, Mami ^{[1
]}

Ono, Kisho ^{[1
]}

Murakami, Jun ^{[4
,5
]}

Aoyama, Eriko ^{[4
]}

Ohyama, Kazumi ^{[1
]}

Asaumi, Jun-ichi ^{[2
]}

Takigawa, Masaharu ^{[4
]}

Okamoto, Kuniaki ^{[1
]}

Calderwood, Stuart K. ^{[6
]}

Kozaki, Ken-ichi ^{[1
]}

Eguchi, Takanori ^{[1
,4
]}

机构：

[1] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Dent Pharmacol, Okayama, Japan

[2] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Oral & Maxillofacial Radiol, Okayama, Japan

[3] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Oral Pathol & Med, Okayama, Japan

[4] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Adv Res Ctr Oral & Craniofacial Sci, Okayama, Japan

[5] Okayama Univ Hosp, Dept Oral Diag & Dentomaxillofacial Radiol, Okayama, Japan

[6] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Div Mol & Cellular Biol, Dept Radiat Oncol, Boston, MA USA

来源：

FRONTIERS IN ONCOLOGY | 2018年 / 8卷

关键词：

ABCG transporter; ABCG1; tumoroids; extracellular vesicle; metastatic cancer; hypoxia; STEM-CELLS; HUMAN-MELANOMA; CHOLESTEROL EFFLUX; GENE-EXPRESSION; EXOSOMES; CHEMORESISTANCE; MICROENVIRONMENT; MACROPHAGE; DELIVERY; HDL;

D O I：

10.3389/fonc.2018.00376

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The ATP-binding cassette transporter G1 (ABCG1) is a cholesterol lipid efflux pump whose role in tumor growth has been largely unknown. Our transcriptomics revealed that ABCG1 was powerfully expressed in rapidly metastatic, aggregative colon cancer cells, in all the ABC transporter family members. Coincidently, genetic amplification of ABCG1 is found in 10-35% of clinical samples of metastatic cancer cases. Expression of ABCG1 was further elevated in three-dimensional tumoroids (tumor organoids) within sternness-enhancing tumor milieu, whereas depletion of ABCG1 lowered cellular aggregation and tumoroid growth in vitro as well as hypoxia-inducible factor 1 alpha in cancer cells around the central necrotic areas in tumors in vivo. Notably, depletion of ABCG1 triggered the intracellular accumulation of extracellular vesicles (EVs) and regression of tumoroids. Collectively, these data suggest that ABCG1 plays a crucial role in tumorigenesis in metastatic cancer and that depletion of ABCG1 triggers tumor regression with the accumulation of EVs and their derivatives and cargos, implicating a novel ABCG1-targeting therapeutic strategy by which redundant and toxic substances may be accumulated in tumors leading to their regression.

引用

页数：16

共 87 条

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