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Clinical & Experimental Metastasis
Published in: Clinical & Experimental Metastasis 6/2013

01-08-2013 | Research Paper

SCUBE3 regulation of early lung cancer angiogenesis and metastatic progression

Authors: Cheng-Hung Chou, Yi-Fang Cheng, Tiing Yee Siow, Amit Kumar, Konan Peck, Chen Chang

Published in: Clinical & Experimental Metastasis | Issue 6/2013

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Abstract

Signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) is strongly expressed in extremely invasive lung carcinoma. We showed in our previous study that SCUBE3 triggers the transforming growth factor-β pathway and subsequently promotes tumor angiogenesis and the epithelial–mesenchymal transition (EMT). However, the role of SCUBE3 in early tumor expansion hasn’t been fully demonstrated in vivo. The present study used dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to temporally assess tumor angiogenesis in SCUBE3-knockdown and control non-small-cell lung carcinoma (NSCLC) cancer cells in the early tumor stage (weeks 1–3). We further evaluated the metastatic potential of the SCUBE3-knockdown and control tumor cells using a circulating tumor cell (CTC) assay. The differences in gene expression profile between these cell lines were determined using microarray analysis. The results show that SCUBE3 knockdown was associated with lower vascular permeability in the tumor and effectively inhibited the metastatic potential of NSCLC, as evidenced by the decreased CTCs in the mice bearing SCUBE3-knockdown tumors. Microarray analysis revealed that several genes involved in angiogenesis and EMT were down-regulated in SCUBE3-knockdown tumors, including matrix metalloproteinases (MMPs) 2, 9, and 14, (MMP-2, MMP-9, and MMP-14, respectively), fibronectin (FN-1), lysyl oxidase (LOX), hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1), early growth response protein 1 (EGR1), and interleukin 8 (IL-8). Together these data suggest that SCUBE3 is a potential target for pharmacological intervention. The findings of the present study also show that differences in vascular permeability precede the CTCs detection, indicating that DCE-MRI may be a sensitive biomarker for assessing tumor invasiveness.
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Metadata
Title
SCUBE3 regulation of early lung cancer angiogenesis and metastatic progression
Authors
Cheng-Hung Chou
Yi-Fang Cheng
Tiing Yee Siow
Amit Kumar
Konan Peck
Chen Chang
Publication date
01-08-2013
Publisher
Springer Netherlands
Published in
Clinical & Experimental Metastasis / Issue 6/2013
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-013-9575-8

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