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Fig. 1 | Journal of Experimental & Clinical Cancer Research

Fig. 1

From: Regulation of heterogeneous cancer-associated fibroblasts: the molecular pathology of activated signaling pathways

Fig. 1

Activated fibroblasts in granulation tissue and carcinoma-associated fibroblasts (CAFs) closely resemble each other regarding their association with the microenvironment. a Hemostasis occurs at the first stage of wound healing, followed by the formation of clots by platelets at the injury site, which changes into fibrin (left). Neutrophils migrate to the granulation tissue, and cytokines are secreted, whereas activated fibroblasts are recruited to the wound-healing tissue. Endothelial progenitor cells are recruited in a manner dependent on the CXCL12-CXCR4 axis, which contributes to angiogenesis (right). During the proliferation stage of wound healing, macrophages infiltrate and initiate phagocytosis for the deposition of new extracellular matrix (ECM) [14]. b Robust neoangiogenesis occurs in the hypoxic tumor microenvironment. Unlike normal fibroblasts, CAFs stimulate tumor progression by secreting CXCL12. CXCL12 derived from CAFs promotes the recruitment of CXCR4-positive endothelial progenitor cells, which are essential for angiogenesis. Invasive metastasis to the bone marrow with high CXCL12 expression triggers CXCR4 activation in circulating tumor cells, which “hijack” the CXCL12-CXCR4 axis for homing to microenvironments that are normally restricted to hematopoietic progenitor cells (HPCs) [16]

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