Table 3.

Macrophage Influence on Cancer Cell Arrest, Extravasation, and Colonization

Primary Tumor	Secondary Site	Macrophage population	Macorphage function	Cancer Interaction	Reference(s)
PyMT breast cancer cells	Lungs	CD11b/Ly6C/VEGFR1/CC R2/CSFR1+ macrophages recruited to secondary site via CCL2 axis	Secretion of VEGFa increases permeability of endothelium	This subset of macrophages is in direct contact with extravasacular breast cancer cells Increased vascular permeability increases metastasis	9,10
Polyoma-middle-T MET-1 cancer cells	Lungs	Recruited monocytes	VEGF secretion by recruited monocytes	VEGF expressing monocytes significantly increase retention of MET-1 cells in the lung	10
MDA-MB-231:4175	Lungs	CD11b+ MAMs	Recruited via CCL2 axis which induces MAM CCL3 secretion and MAM retention via CCL3/CCR1 axis	The CCL3/CCR1 axis leads to direct binding of tumor cells to MAMs via α4 integrin binding to VCAM-1 in breast cancer cells	11
B16 Melanoma	Lungs	CCR2+ BMDM	Engulf cytoplasts and upregulate adhesion receptors VCAM-1, CD-38, CD-63, CD-88, CMKLR-1, and CD-155	Melanoma cells secrete shear-induced “cytoplasts” that initiate pro-tumoral immune cell recruitment Lack of macrophages results in recruitment of anti-tumoral immune cells	12
MMTV-PyMT indced mammary tumor cells	-- Lungs	TAMs	BMDMs are recruited via CSF-1 gradients and secrete EGF to aid tumor cell invasion MAMs are recruited to the lung in a CSF1 dependent manner	Secrete CSF-1 to recruit macrophages. Migrate along EGF gradients produced by macrophages. Intravasate due to this mechanism	9,25,52
Lung-tropic breast cancer cells (MDA231-LM2-175)	Lungs	CD11b+/VLA4+ BMDMs	Macrophages bind to VCAM-1 with α4 integrins	Binding of breast cancer VCAM-1 to α4 activates pro migratory and survival PI3K-AKT	41,42
--	--	Macrophage activation	Promote endothelial expression of VCAM-1	Aids TAM localization and upregulates α4 integrins in macrophages which tethers breast cancer cells	42
MB49 murine bladder cancer	Lungs	BMDM	Arrive to extravasation site before cancer cells and produce CCL2, COX-2, MMPs and IL-6 Depletion of ET-1 from cancer cells decreased macrophage influx to the lung	Secondary tumor growth, not primary tumor, is affected by ET-1 expression ET-1 recruits macrophages to secondary site to aid immune response and angiogenesis	50,51
Pancreatic Ductal Carcinoma (PDAC)	Liver	BMDM	Recruited to liver and secrete granulin which promotes myofibroblast differentiation	Myofibroblasts secrete periostin which promotes PDAC metastatic growth via αVβ3-AKT/PKB signaling	54