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Morphological Effects on Expression of Growth Differentiation Factor 15 (GDF15), a Marker of Metastasis
被引：30
|作者：
Yong, Koh Meng Aw
[1
]
Zeng, Yu
[1
]
Vindivich, Donald
[1
]
Phillip, Jude M.
[2
,3
]
Wu, Pei-Hsun
[2
,3
]
Wirtz, Denis
[2
,3
]
Getzenberg, Robert H.
[1
,4
,5
]
机构：
[1] Johns Hopkins Univ, Sch Med, Dept Urol, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD USA
[3] Johns Hopkins Univ, Johns Hopkins Phys Sci Oncol Ctr, Baltimore, MD USA
[4] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA
[5] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA
关键词：
MACROPHAGE INHIBITORY CYTOKINE-1;
PROGNOSTIC MARKER;
GENE-EXPRESSION;
CELL-CULTURE;
IN-VIVO;
BONE;
P38;
DISRUPTION;
CHONDROGENESIS;
PROLIFERATION;
D O I：
10.1002/jcp.24458
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ;
090102 ;
摘要：
Cancer cells typically demonstrate altered morphology during the various stages of disease progression as well as metastasis. While much is known about how altered cell morphology in cancer is a result of genetic regulation, less is known about how changes in cell morphology affect cell function by influencing gene expression. In this study, we altered cell morphology in different types of cancer cells by disrupting the actin cytoskeleton or by modulating attachment and observed a rapid up-regulation of growth differentiation factor 15 (GDF15), a member of the transforming growth factor-beta (TGF-) super-family. Strikingly, this up-regulation was sustained as long as the cell morphology remained altered but was reversed upon allowing cell morphology to return to its typical configuration. The potential significance of these findings was examined in vivo using a mouse model: a small number of cancer cells grown in diffusion chambers that altered morphology increased mouse serum GDF15. Taken together, we propose that during the process of metastasis, cancer cells experience changes in cell morphology, resulting in the increased production and secretion of GDF15 into the surrounding environment. This indicates a possible relationship between serum GDF15 levels and circulating tumor cells may exist. Further investigation into the exact nature of this relationship is warranted. J. Cell. Physiol. 229: 362-373, 2014. (c) 2013 Wiley Periodicals, Inc.
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页码：362 / 373
页数：12
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