S100 chemokines mediate bookmarking of premetastatic niches

Abstract

Primary tumours release soluble factors, including VEGF-A, TGFβ and TNFα, which induce expression of the chemokines S100A8 and S100A9 in the myeloid and endothelial cells within the lung before tumour metastasis. These chemokine-activated premetastatic niches support adhesion and invasion of disseminating malignant cells, thereby establishing a fertile habitat for metastatic tumours.

Figure1

Establishment of a premetastatic niche by tumour cells. Primary tumour cells secrete pro-inflammatory factors such as VEGF-A, TGFβ and TNFα, which induce selective expression of chemoattractants S100A8 and S100A9 by lung VE-cadherin⁺-endothelial cells (blue) and Mac1⁺-myeloid cells (green). S100A8 and S100A9 expressed by the endothelial cells recruit Mac1⁺-myeloid cells, which set the stage for the arrival and docking of S100-responsive tumour cells (red) to the permissive lung tissue.