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Growth differentiation factor 15 (GDF15) in cancer cell metastasis: from the cells to the patients

  • Molecules in Metastasis
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Abstract

Growth differentiation factor 15 (GDF15), a member of the transforming growth factor β superfamily, has been postulated to be implicated in cancer cell metastasis although its role has not been fully elucidated yet. The purpose of this review is to clarify the role of GDF-15 in cancer cell metastasis based on current advances in the field. The studies were divided into those involving evaluation of GDF15 expression in the serum or tissue of cancer patients, and those involving in vitro experiments in cancer cell lines or in vivo experiments in animal models. GDF15 was shown to be elevated in the serum or tissues of cancer patients with its expression being correlated with decreased survival. Moreover, most in vitro and in vivo studies also corroborated a metastasis-promoting role for GDF15. However, there were a few studies, where GDF15 was shown to suppress the metastatic properties of cells. As, GDF15 has been known for its pleiotropic effects, it is not surprising to behave differently in different types of cancer. Thus, GDF15 has the potential of not only being a useful metastasis biomarker, but also a promising therapeutic target against cancer cell metastasis in many cancer types.

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Abbreviations

AFP:

Alpha fetoprotein

ESCC:

Esophageal carcinomas

ERK:

Extracellular signal-regulated kinase

CA19-9:

Carbohydrate antigen 19 − 9

CAF:

Cancer associated fibroblasts

CDK:

Cyclin-dependent kinase

CEA:

Carcinoembryonic antigen

CRC:

Colorectal cancer

CREB-1:

CAMP Responsive Element Binding Protein

CSF:

Cerebrospinal fluid

EGR-1:

Early Growth Response − 1

EMT:

Epithelial-mesenchymal transition

ER:

Estrogen receptor

ESCC:

Esophageal squamous cell carcinoma

FAK:

Focal adhesion kinase

GBM:

Glioblastoma multiform

GDF-15:

Growth Differentiation Factor-15

GDNF:

Glial cell-derived neurotrophic factor

GFRAL:

GDNF Family Receptor Alpha Like receptor

HCC:

Hepatocellular carcinoma

ICTP:

Cross-linked carboxy-terminal telopeptide of type I collagen (ICTP)

IL-6:

Interleukin-6

LC:

Liver cirrhosis

TGF-β:

Transforming Growth Factor-β

PARVA:

Alpha-parvin

PDF:

Prostate Derived Factor

PD-L1:

Programmed death-ligand-1

PINP:

Amino-terminal propeptide of type I procollagen (PINP).

PR:

Progesterone receptor

PSA:

Prostate-specific antigen

ROCK-1:

Rho-associated protein kinase-1

RSU-1:

Ras suppressor-1

MIC-1:

Macrophage Inhibitory Cytokine-1

MMP-13:

matrix metalloproteinase-13

NAG-1:

Non Steroidal Anti Inflammatory Drug – activated gene

PINCH-1:

Particularly Interesting New Cystein Histidine protein-1

PLAB:

Placental bone morphogenetic protein

PTGFB:

Placental Transforming Growth Factor Beta

RSU-1:

Ras suppressor-1

SCC:

Squamous Cell Carcinoma antigen

TRAMP:

Transgenic Adenocarcinoma of Mouse Prostate

OSCC:

Oral Squamous Cell Carcinoma

YAP:

Yes associated protein

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Authors and Affiliations

  1. Biological Sciences Program, Department of Life Sciences, School of Sciences, European University Cyprus, Nicosia, Cyprus

    Anna Spanopoulou

  2. Biomedical Sciences Program, Department of Life Sciences, School of Sciences, European University Cyprus, 6, Diogenis Str, Engomi, 2404, Nicosia, Cyprus

    Vasiliki Gkretsi

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  1. Anna Spanopoulou
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Spanopoulou, A., Gkretsi, V. Growth differentiation factor 15 (GDF15) in cancer cell metastasis: from the cells to the patients. Clin Exp Metastasis 37, 451–464 (2020). https://doi.org/10.1007/s10585-020-10041-3

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