Table 1.
Paracrine Factors Observed in Wound Healing and Tumorigenesis
| Paracrine factor | Role in wound healing | Role in tumorigenesis | ASC-mediated cancer type | Differentially expressed with age |
|---|---|---|---|---|
| CCL5 | Macrophage recruitment | Immune cell recruitment, stimulates angiogenesis, modulates ECM, tumor cell proliferation, enhances tumor cell migration and invasiveness | Breast cancer [80] | Unknown |
| GDF11 | Activates fibroblasts in hemostasis and proliferation phases, activates platelets in clot formation, increases angiogenesis/cell proliferation/cell migration/ECM production | Induces tumor suppressive and oncogenic properties | N/A | Unknown |
| IL-6 | Regulates chronic inflammation, macrophage recruitment, macrophage polarization | Chronic inflammatory environment can lead to tumor development, enhances migration and invasiveness of tumor cells | Breast Cancer [81,82] | ✓ |
| IL-8 | Stimulates angiogenesis, granulocyte recruitment | EMT, neutrophil migration | Breast cancer [81,82] | Unknown |
| LEP | Stimulates angiogenesis, cell proliferation, and differentiation, keratinocyte migration | Increases TNF-α and ROS production, increases MCP-1 expression, increases endothelial cell proliferation and migration, increases tumor cell invasion and metastasis | ER+ breast cancer [82] | ✓ |
| MCP-1 | Macrophage recruitment | Involved in tumor progression and metastasis | Bladder cancer, Breast cancer [81], Melanoma [83] | Unknown |
| PAI-1 | Keratinocyte migration, fibroblast migration and fibroblast-myofibroblast differentiation | Tumor cell migration and metastasis, macrophage migration and polarization, inhibits fibrinolysis, cell adhesion | Breast cancer [80], Colon cancer [80] | Unknown |
| PDGF | Stimulates chemotaxis, proliferation, and new gene expression in macrophages and fibroblasts | ECM remodeling | Breast cancer [84] | ✓ |
| SDF-1 | Chemotaxis of ASCs | SDF-1-CXCR4 expression associated with EMT phenotype, contribution to hormone independence via SDF-1-CXCR4-ER-α crosstalk | ER+ breast cancer [81] | ✓ |
| TGF-β1 | ECM production and remodeling | Promotes EMT, increases tumor cell motility and metastasis, ECM remodeling | Breast cancer [81] | ✓ |
| TNF-α | Upregulated in inflammatory phase, ASCs stimulate macrophages to secrete TNF-α | Development of tissue architecture for tumor growth and metastasis, EMT with long-term exposure to TNF-α | ER+ breast cancer [80], Breast cancer [84] | ✓ |
| VEGF | Stimulates collagen deposition, angiogenesis, and epithelization | Stimulates angiogenesis, enhances tumor cell invasiveness and migration | Melanoma [83], Breast cancer [81,84] | ✓ |
N/A indicates that no information was found in the literature that supports the role of GDF11 in ASC-mediated cancer. The ✓ indicates that patient age plays a role in the expression of the specified paracrine factor.
ASC, adipose stromal/stem cell; ECM, extracellular matrix; EMT, epithelial to mesenchymal transition; ROS, reactive oxygen species; LEP, leptin; MCP-1, monocyte chemoattractant protein 1; PDGF, platelet-derived growth factor; TGF, transforming growth factor; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor.