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] |