演題抄録

FACO International Workshop

開催概要
開催回
第53回・2015年・京都
 

Clinical significance of GPNMB and its association with HER2 in breast cancer

演題番号 : FWS11-3

[筆頭演者]
Futamura Manabu:1 
[共同演者]
Morimitsu Kasumi:1、Mori Ryutaro:2、Yoshida Kazuhiro:2

1:Dept. of Breast & Molecular Oncology, School of Medicine, Gifu University、2:Dept. of Surgical Oncology, School of Medicine, Gifu University

 

Glycoprotein non-metastatic B (GPNMB) is a type I transmembrane protein, which is isolated from differential expression assay using metastatic melanoma cells. It's supposed to be associated with cell invasion and motility particularly in breast cancer cells. Here we investigated the role of GPNMB in breast cancer. First we checked expression of GPNMB by RT-PCR and western blot in several cancer cell lines followed by establishment of GPNMB measurement by ELISA. GPMNB expressed in breast (5/6:83%), gastric (3/6:50%), colon (1/7:14.3%) cancer cell lines. Of breast cancer cell lines, GPNMB was highly expressed in SK-BR3 (HER2 positive), BT474 (HER2/ER positive), MDA-MB-157 (Triple negative) cells. Shed GPNMB in culture medium was measurable and correlated with expression of each cell line. Next we evaluated serum GPNMB in patients with breast [n=164; primary 119, metastatic 43), gastric (n=38), and colorectal (n=50) cancer in our institute from 2011.9-2014.2.] Serum GPNMBs were 9.403, 5.751, 6.550 ng/ml, respectively. GPNMB for breast cancer patients was statistically higher than those by colorectal cancer patients (p=0.018). Of breast cancer patients, GPNMB for HER2-type patients was higher than those for Luminal type and DCIS patients (p=0.0386, p=0.0195, respectively). Those for triple negative patients was also higher than those for DCIS patients (p=0.0459). Interestingly, serum GPNMB was dramatically reduced in accordance with chemotherapy in some patients. Based on these clinical observations, we further investigated relationship between GPNMP and HER2 in vitro. Blockage of GPNMB induced not only HER2 but also EGFR expression. On the other hand, inhibition of HER2 by trastuzumab (Tra) increased expression of GPNMB. Depletion of GPNMB increased sensitivity of Tra, suggesting that GPNMB may play an important role in crosstalk of signal transduction for breast cancer. These notions may suggest a novel therapeutic strategy to overcome HER2 positive breast cancer.

キーワード

臓器別:乳腺

手法別:トランスレーショナルリサーチ

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