Abstract
Primary tumours secrete many cytokines and chemokines including CCL2, VEGF, TNFα, and TGF-β. In the natural course of primary tumour growth, these factors stimulate bone marrow cells and tissue-resident cells including immune cells and endothelial cells in the distant host tissues. Despite ubiquitously spreading in blood vessels, the secreted factors from primary tumours mediate discrete hyperpermeability foci by several overlapping cascades such as S100A8-SAA3-TLR4/MD-2 and VEGF-FAK-E-selectin. The former is that these secreted factors stimulate CCR2 in potentially hyperpermeable areas, further inducing the secretion of SAA3 and S100A8, which increase vascular permeability via TLR4/MD-2. The latter is that tumour-derived VEGF generates the permeable foci with E-selectin upregulation through endothelial FAK in the premetastatic lungs. Blocking the cascade of the permeability in hyperpermeability regions before metastasis results in the reduction of tumour cell homing. Thus, it is an advantage to target very early metastatic or premetastatic phase.
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Hiratsuka, S. (2016). Establishment of Diagnosis for Early Metastasis. In: Miyasaka, M., Takatsu, K. (eds) Chronic Inflammation. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56068-5_16
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DOI: https://doi.org/10.1007/978-4-431-56068-5_16
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