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. 2022 Oct 13;31(19-20):579–592. doi: 10.1089/scd.2021.0280

FIG. 2.

FIG. 2.

Cytokines released during the phases of acute wound healing are also present during cancer hallmark acquisition. (A) Tissue injury activates platelet recruitment to the site of injury, where a temporary fibrin clot stops blood vessel hemorrhage. Platelets release a heterogeneous mix of growth factors and cytokines (PDGF, TGF-β, IL-8, SDF-1, CXCL4, bFGF, and VEGF) that aid in the repair process. (B) The inflammatory phase begins with the influx of neutrophils followed by macrophages to the wound bed. Neutrophils begin the phagocytosis of debris in the wound and release chemokines (MCP-1 and CCL5) that recruit macrophages to the wound. With the reduction of neutrophils around days 2–4, macrophages become the dominant inflammatory cells in the wound. They not only protect the wound from foreign microorganisms, but they also release growth factors, chemokines, and cytokines (VEGF, bFGF, PDGF, and TNF-α) that aid in wound repair. (C) Around days 3–10, fibroblasts are recruited to the wound, where they contribute to the formation of a temporary ECM. (D) Several months to years after injury, cells leave the wound or undergo apoptosis. ECM is broken down by MMPs and metalloproteinase tissue inhibitors (TIMPs). Type III collage that was deposited during the proliferation phase is degraded and replaced by a more permanent Type I collagen. Growth factors and cytokines highlighted in the 4 phases of wound healing are also actively involved in the hallmarks of cancer outlined by Hanahan and Weinberg [10]. Parallels in secreted factors of wound healing are observed in the following cancer hallmarks: tumor and repair promoting inflammation, sustaining proliferative signaling, and angiogenesis. The color scheme linking the association between the hallmarks of cancer and specific paracrine factors can be referenced using the figure legend. This figure was created using BioRender.com. ECM, extracellular matrix; MMP, matrix metalloproteinase; PDGF, platelet-derived growth factor; TGF-β, transforming growth factor beta; bFGF, basic fibroblast growth factor; VEGF, vascular endothelial growth factor; MCP-1, monocyte chemoattractant protein 1.