Fig. (3) Potential interplay between macrophages, mammary epithelial cells and HCMV in breast cancer. HCMV infection of HMEC induces their priming towards epithelial transformation, by activation of several signaling pathways (Akt, Myc, Ras). HCMV also favors macrophages differentiation towards M2 phenotype. HMEC produces CFS-1, that will enhance cell transformation. This creates a favorable microenvironment, in which infected HMEC produce CCL-2 that promotes TAMs differentiation. In turn, TAMs secrete EGF, that promote breast cancer cells proliferation. Once HMEC had been transformed, they produce GM-CSF, which activate macrophages. In turn, TAMs secrete CCL18, that promotes the epithelial-mesenchymal transition (EMT) of breast cancer cells. This interplay favors cells activations and transformations, leading toward increased metastasis of breast cancer cells and increased tissue infiltration by TAMs. BCCs: Brest Cancer Cells ; CSF: Colony Stimulating Factor ; EMT: epithelial-mesenchymal transition ; HMEC: Human Mammary Epithelial Cells ; MBCs: Metastatic Breast Cancer cells ; TAMs: Tumor Associated Macrophages ; Bcl: B-cell lymphoma encoded protein ; CCL : C-C Motif Chemokine Ligand ; EGF: Epidermal Growth Factor ; GM: Granulocyte Macrophage ; HCMV : Human Cytomegalovirus ; IL: Interleukin ; NOS: NO Synthase ; TNF: Tumor Necrosis Factor.

Back to Article