Table 2 Characteristics of cytokines/growth factors differentially expressed between benign and malignant seroma fluid

Up-regulated in malignant vs. benign

 GRO

JAK/STAT, PI3K/AKT, MAPK, PLC/PKC (KEGG Kyoto Encyclopedia of Genes and Genomes 2015)

Attracts and activates granulocytes (Owen and Mohamadzadeh 2013)

Supports growth of triple-negative breast cancer cells (Hartman et al. 2013)

Involved in cancer chemo-resistance and metastasis (Acharyya et al. 2012)

 ENA-78/CXCL5

JAK/STAT, PI3K/AKT, MAPK, PLC/PKC (KEGG Kyoto Encyclopedia of Genes and Genomes 2015)

Chemoattractant and activator of neutrophil function (Owen and Mohamadzadeh 2013)

Promotes breast cancer cells migration, invasion (Hsu et al. 2013)

Regulates cancer stem cells (Liu et al. 2011)

 TIMP-2

–

Inhibits metalloproteinase activity (Ellerbroek and Stack 1999)

Facilitates cell-surface activation of pro-MMP-2 (Lu et al. 2004; Shen et al. 2010)

TIMP-2 regulates MMP-2-mediated breast cancer cell transmigration through lung microvascular endothelial cells (Shen et al. 2010)

High levels of TIMP-2 correlate with adverse prognosis in breast cancer (Remacle et al. 2000)

Down-regulated in malignant vs. benign

 IGFBP-1

–

Binds to IGFs and can either inhibit or stimulate their growth promoting effects (Lee et al. 1993)

Inhibits IGF-mediated breast cancer proliferation (Yee et al. 1994)

Inhibits breast cancer cell motility (Zhang and Yee 2002)

 IL-3

JAK/STAT, MAPK, PI3K/AKT

NF-κB (Reddy et al. 2000)

Haemopoietic growth factor which stimulates the production and functional activity of various blood cell types (Korpelainen et al. 1996)

Increases tumor immunogenicity-promotes macrophage infiltration and promotes development of tumor reactive cytotoxic T-cells^a (Pulaski et al. 1996)

 IFN-γ

JAK/STAT (Schroder et al. 2004)

Important in host defense mechanisms

Has antiviral, immunoregulatory and proinflammatory activities (Schroder et al. 2004)

Inhibits cell growth (Gooch et al. 2000)

 FGF-9

MAPK, PI3K/AKT, PLC/PKC (Goetz and Mohammadi 2013)

Important for the regulation of embryonic development, cell proliferation, differentiation and migration (Goetz and Mohammadi 2013)

Induces cancer stem cell expansion (Fillmore et al. 2010)

 IL-16

Ca²⁺, PIP₃, SAPK (Krautwald 1998)

Chemotactic for CD4⁺ T lymphocytes, monocytes, and eosinophils

Promotes T-cell proliferation (Wilson et al. 2004)

Promotes cell proliferation^a (Atanackovic et al. 2012)