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Table 2 Factors of secondary soil-to-seed signals involved in promoting metastasis

From: Factors involved in cancer metastasis: a better understanding to “seed and soil” hypothesis

Metastatic sites Molecules Cell type Underlying mechanisms Cancer type Ref
Lung POSTN Stromal cells POSTN expressed in stroma recruits Wnt ligands and thereby increases Wnt signaling in cancer stem cells. Breast cancer [27]
MMP9/
VEGFR-1TK
Macrophages
Endothelial cells
MMP9 is specifically induced in pre-metastatic lung endothelial cells and macrophages, thus promoting metastasis. Lung cancer
Melanoma
[119]
α4-integrins Macrophages Macrophage binding to receptor VCAM-1 in cancer cells transmits survival signals. Breast cancer [120]
CCL5 Endothelial cells CCL5 expression enhances lung colonization by recruiting innate immune cells to the metastatic microenvironment. Colorectal cancer [121]
S100A8/
S100A9
Undetermined Upregulation of chemoattractants and recruitment of myeloid cells facilitate the pre-metastatic niche formation. Lung cancer
Melanoma
[122]
IFN-γ/
MMP9
Myeloid cells Remodel the pre-metastatic lung into an inflammatory and proliferative environment, thus diminishes immune protection. Breast cancer [123]
Versican Myeloid Progenitor Cells Versican induces mesenchymal to epithelial transition of metastatic cancer cells by attenuating phospho-Smad2 levels. Breast cancer [124]
Leukotrienes Neutrophils Neutrophil-derived leukotrienes aid lung colonization by selectively expanding cancer cells with tumorigenic potential. Mammary tumor [125]
PHD proteins T cells PHD proteins function in T cells promoting lung colonization by establishing an immunologically tolerant metastatic niche. Melanoma [126]
Liver Undetermined Hepatic stellate cells (HSCs) HSCs play a critical role in mediating pro-metastatic niche. Colorectal cancer [127]
Granulin Metastasis-associated macrophages (MAMs) MAMs activate resident hepatic stellate cells (hStCs) to transition into myofibroblasts, thus promoting metastasis. PDAC [128]
MIF Hepatic sinusoidal endothelial cells (HHSECs) MIF enhances migration and EMT and facilitates proliferation and apoptotic resistance in cancer cells. Colorectal cancer [129]
Angiopoietin-like 6 Undetermined Angiopoietin-like 6 accumulates in normal vessels and interacts with the cancer cell, thus promoting colonization. Colorectal cancer [130]
LSECtin Undetermined LSECtin expressed in liver promotes colon carcinoma cell adhesion and migration. Colorectal cancer [131]
Bone Fibronectin BMDCs BMDCs upregulate fibronectin in resident fibroblasts, facilitating the pre-metastatic niche formation. Lung cancer
Melanoma
[132]
N-cadherin Osteogenic cell Osteogenic niche activates the mTOR pathway in cancer cells, promoting bone colonization. Breast cancer [133]
CCL5/MMP Osteocytes Upregulation of CCL5 and MMP in osteocytes promotes cancer invasion and growth. Prostate cancer [134]
Extracellular ATP adenosine Osteocytes ATP and adenosine released by osteocytes promotes cancer cell migration, growth and metastasis. Breast cancer [135]
Brain Extracellular matrix Astrocytes Extracellular matrix secreted by astrocyte stimulates cancer cell proliferation and EMT process. Prostate cancer [136]
IL-23 Astrocytes Astrocyte-derived molecules facilitate metastasis by enhancing invasion of cancer cell. Melanoma [137]
Exosomal miRNAs Astrocytes Astrocyte-derived factors induce PTEN loss in cancer cells, promoting brain metastasis outgrowth. Breast cancer [138]