Disialyl GD2 ganglioside suppresses ICAM-1-mediated invasiveness in human breast cancer MDA-MB231 cells

被引：14

作者：

Kwon, Kyung-Min ^{[1
,2
]}

Chung, Tae-Wook ^{[3
]}

Kwak, Choong-Hwan ^{[1
]}

Choi, Hee-Jung ^{[3
]}

Kim, Kyung-Woon ^{[4
]}

Ha, Sun-Hyung ^{[1
]}

Cho, Seung-Hak ^{[5
]}

Lee, Young-Choon ^{[6
]}

Ha, Ki-Tae ^{[3
]}

Lee, Moon-Jo ^{[7
]}

Kim, Cheorl-Ho ^{[1
,8
]}

机构：

[1] Sungkyunkwan Univ, Mol & Cellular Glycobiol Unit, Dept Biol Sci, Seoburo 2066, Suwon 16419, Gyunggi Do, South Korea

[2] Davinch K Co Ltd, Res Inst, B1603-3,606 Seobusaet Gil, Seoul 153719, South Korea

[3] Pusan Natl Univ, Div Appl Med, Sch Korean Med, Yangsan, Gyeongsangnam D, South Korea

[4] Natl Inst Anim Sci, RDA, Anim Biotechnol Div, Wanju Gun, Jeollabuk Do, South Korea

[5] Korea Natl Inst Hlth, Div Enter Dis, Ctr Infect Dis Res, Heungdeok Gu 363951, Cheongju, South Korea

[6] Dong A Univ, Dept Biotechnol, Busan 604714, South Korea

[7] Dong Eui Inst Technol, Dept Herb Sci, 54 Yangji Ro, Busan 47230, South Korea

[8] SAIHST, Dept Med Device Management & Res, Seoul 06351, South Korea

来源：

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES | 2017年 / 13卷 / 03期

基金：

新加坡国家研究基金会;

关键词：

Ganglioside GD3 synthase; Breast cancer; MDA-MB231; Intracellular adhesion molecule-1; GM2/GD2 synthase (beta 4-GalNc T); Invasion; ADHESION MOLECULES; GENE-EXPRESSION; MATRIX-METALLOPROTEINASE-9; EXPRESSION; G(D3) SYNTHASE; GROWTH; ICAM-1; DISIALOGANGLIOSIDE; METASTASIS; ACTIVATION; MDA-MB-231;

D O I：

10.7150/ijbs.16903

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

disialoganglioside GD3 has been considered to be involved in tumor progression or suppression in various tumor cells. However, the significance of the biological functions of GD3 in breast cancer cells is still controversial. This prompted us to study the possible relationship(s) between GD3 expression and the metastatic potential of a breast cancer MDA-MB231 cells as an estrogen receptor negative (ER-) type. The human GD3 synthase cDNA was transfected into MDA-MB231 cells, and G-418 bulk selection was used to select cells stably overexpressing the GD3 synthase. In vitro invasion potentials of the GD3 synthase over-expressing cells (pc3-GD3s) were significantly suppressed when compared with control cells. Expression of intercellular adhesion molecule-1 (ICAM-1; CD54) was down-regulated in the pc3-GD3s cells and the decrease in ICAM-I expression is directly related to the decrease in invasiveness of the pc3-GD3s cells. Another type of ER negative SK-BR3 cells exhibited the similar level of ICAM- 1 expression as MDA-MB231 cells, while the ER positive MCF-7 cells (ER+) showed the increased expression level of ICAM-1. Then, we investigated signaling pathways known to control ICAM- 1 expression. No difference was observed in the phosphorylation of ERK and p38 between the pc3-GD3s and control cells (pc3), but the activation of AKT was inhibited in pc3-GD3s, and not in the control ( pc3). In addition, the composition of total gangliosides was changed between control ( pc3) and pc3-GD3s cells, as confirmed by HPTLC. The pc3-GD3s cells had an accumulation of the GD2 instead of the GD3. RT-PCR results showed that not only GD3 synthase, but also GM2/GD2 synthase (beta 4-GalNc T) expression was increased in pc3-GD3s cells. Overexpression of GD3 synthase suppresses the invasive potential of human breast cancer MDA-MB-231 cells through down-regulation of ICAM- 1 and the crucial pathway to allow the apoptotic effect has been attributed to accumulation of the GD2 ganglioside. ER has been linked to the ICAM- 1 expression with GD3 to GD2 conversion in human breast cancer cells. This is the first finding of the endogenous sialyltransferase functions in tumor cells.

引用

页码：265 / 275

页数：11

共 44 条

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