Effects of VEGFR1+ hematopoietic progenitor cells on pre-metastatic niche formation and in vivo metastasis of breast cancer cells

Abstract

The pre-metastatic niche has been shown to play a critical role in tumor metastasis, and its formation is closely related to the tumor microenvironment. However, the underlying molecular mechanisms remain unclear. In the present study, we successfully established a mouse model of lung metastasis using luciferase-expressing MDA-MB-435s cells. In this model, recruitment of vascular endothelial growth factor receptor-1 (VEGFR1) + CD133 + hematopoietic progenitor cells (HPCs) was gradually increased in lung but gradually decreased after the formation of tumor colonies in lung. We also established a highly metastatic MDA-MB-435s (MDA-MB-435s-HM) cell line from the mouse model. Changes in protein profiles in different culture conditions were investigated by protein microarray analysis. The levels of CXC chemokine ligand 16, interleukin (IL)-2Rα, IL-2Rγ, matrix metalloproteinase (MMP)-1, MMP-9, platelet-derived growth factor receptor (PDGFR)-α, stromal cell-derived factor (SDF)-1α, transforming growth factor (TGF)-β, platelet endothelial cell adhesion molecule (PECAM)-1 and vascular endothelial (VE)-cadherin were significantly greater (> fivefold) in the culture medium from MDA-MB-435s-HM cells than in that from MDA-MB-435s cells. Moreover, the levels of MMP-9, PDGFR-α, and PECAM-1 were significantly greater in the co-culture medium of MDA-MB-435s-HM cells and CD133 + HPCs than in that from MDA-MB-435s-HM cells. Differentially expressed proteins were validated by enzyme-linked immunosorbent assay, and expression of their transcripts was confirmed by quantitative real-time polymerase chain reaction. Moreover, inhibition of MMP-9, PDGFR-α, and PECAM-1 by their specific inhibitors or antibodies significantly decreased cell migration, delayed lung metastasis, and decreased recruitment of VEGFR1 + CD133 + HPCs into lung. Intra-hepatic growth of HPCs enhanced the invasive growth of MDA-MB-435s-HM cells in the liver. Our data indicate that VEGFR1 + CD133 + HPCs contribute to lung metastasis. Electronic supplementary material The online version of this article (10.1007/s00432-018-2802-6) contains supplementary material, which is available to authorized users.

XIAOPI formula inhibits the pre-metastatic niche formation in breast cancer via suppressing TAMs/CXCL1 signaling

“…Six weeks after inoculation of 4 T1 cells, HSPCs were found to appear a sharp decrease. This was consistent with the findings of Liu et al that HSPCs population was gradually decreased after the formation of tumor colonies in target organs of metastasis [19]. Moreover, TAMs co-inoculation was found to promote HSPCs recruitment and MDSCs differentiation, which was blocked by XIAOPI formula and CXCL1 knockdown.…”

“…Recent studies suggested that PMN formation is a critical factor determining the site and time of cancer metastasis [19,20]. Drugs targeting PMN could represent a novel therapeutic strategy in improving clinical outcomes of cancer patients.…”

MicroRNA-3163 targets ADAM-17 and enhances the sensitivity of hepatocellular carcinoma cells to molecular targeted agents

“…Hepatic portal vein injection was used to inoculate HCC cells into the liver of nude mice, simulating the recurrence or metastasis of HCC cells in patients. In addition Meng et al [70][71][72] established a research model for the invasion of malignant tumor cells in the liver of nude mice. Li et al 73 developed a breast cancer lung metastasis model in nude mice.…”

Role of platelets and breast cancer stem cells in metastasis

“…The miRNAs found in the TME can come from platelets or platelet microparticles (PMPs). PMPs are the most abundant microparticles in the blood and contain, in addition to miRNAs[ 53 ], several EMT-promoting factors, including basic fibroblast growth factor (bFGF), fibroblast growth factor (FGF)[ 54 ], platelet-derived growth factor (PDGF)[ 55 ], hepatocyte growth factor (HGF)[ 56 ], TGF-β[ 57 ], vascular endothelial growth factor (VEGF)[ 58 ] and brain-derived neurotrophic factor/tropomyosin-related kinase (BDNF/TRK)[ 59 ].…”