Table 1 The distinct characteristics among different organ metastasis
From: New insights into the correlations between circulating tumor cells and target organ metastasis
Organ | Category | Key factor | Mechanism | Primary cancer | Ref. |
|---|---|---|---|---|---|
Brain | Characteristics of CTCs | Nestin, CD133 and Cd44 | Markers of circulating tumor stem cells, indicating stronger metastatic potential | Breast cancer and TNBC | |
CD44v6 | Activate the EMT process | Small cell lung cancer | |||
HER2, EGFR, HPSE and Notch1 | Highly invasive phenotype of CTCs | Breast cancer | |||
RAC1 | Regulate the motility of CTCs | LUAD | |||
Nrf2 | Mediate Keap1-Nrf2-ARE pathway and drive anti-oxidant gene expression | Lung cancer | |||
RPL/RPS | Be associated with ribosome production, translation and metabolism of CTCs | Melanoma | |||
SEMA4D | Activate Rho pathway, which facilitates CTCs migration across the BBB | Breast cancer | |||
COX2 | Activate MMP-1 to break down endothelial cell connections | TNBC | |||
ST6GALNAC5 | Enhance the adhesion of CTCs to brain endothelial cells | Breast cancer | |||
MYC | Up-regulate GPX1 expression to alleviate the killing effect of oxidative stress | Breast cancer | |||
Extracellular vesicles | miR-105 | Target ZO-1, which increases vascular permeability of the BBB | Breast cancer | ||
miR-19a | Down-regulate PTEN and up-regulate CCL2 to promote the migration of CTCs | Breast cancer | |||
Microenvironment | Anti-PA serpins | Inhibit PAs-mediated cell apoptosis | Breast cancer | ||
PCDH7 | Assist cGAMP to secrete inflammatory cytokines such as IFN-α and TNF | Breast cancer | |||
Lung | Characteristics of CTCs | FADS3 | Enhance cell membrane fluidity | Breast cancer | |
LT receptors (BLT2 and CysLT2) | Increase tumorigenicity in lung PMN | Breast cancer | |||
ICAM-1 | Drive CTC cluster formation and lead to lung metastasis | TNBC | |||
VCAM-1 | Activate VCAM-1-Ezrin-PI3K/Akt pathway | Breast cancer | |||
Periostin and tenascin C | Maintain cancer cell stemness | Breast cancer | |||
Exosome | miR-105 | Break the monolayer vascular endothelial barrier by degrading ZO-1 | Breast cancer | ||
Integrins α6β4 and α6β1 | Up-regulate the expression of a metastasis-promoting factor, S100A4 | Breast cancer | |||
miR-122 | Down-regulate glycolytic enzyme pyruvate kinase to inhibit glucose uptake | Breast cancer | |||
Microenvironment | VEGFR1+ BMDCs | Combine with TDSFs to increases MMP-9 expression | Melanoma | ||
S100A8 and S100A9 | Massive recruitment of myeloid cells | Â | |||
lysyl oxidase | Cross-linked to type IV collagen in the lung to recruit myeloid cells | Breast cancer | |||
CCR2+ inflammatory monocytes | Secrete VEGF to assist survival of CTCs | Muscle-invasive bladder cancer | |||
Bone marrow-derived neutrophils | Secrete proteases to proteolytically destroy the antitumor factor Tsp-1. | Â | |||
TGF-β1 and periostin | Awaken dormant tumor cells | Breast cancer | |||
Liver | Characteristics of CTCs | Hybrid CTCs | Prefer intrahepatic metastasis | Hepatocellular carcinoma | |
Mesenchymal CTCs | Prefer extrahepatic metastasis | Hepatocellular carcinoma | |||
CD133 | Show obvious preference for liver metastasis | Lung caner | |||
CD110 | TPO-Induced metabolic reprogramming | Colorectal cancer | |||
Extracellular vesicles | MIF | Induce Kuppfer cells to secret TGF-β | Pancreatic ductal adenocarcinoma | ||
Integrin αvβ5 | Stimulate Kupffer cells to express proinflammatory S100A8 and S100P | Breast cancer | |||
miR-122-5p | Facilitate the migration and EMT of CTCs | Lung caner | |||
miR-25-3p, miR-638, miR-663a, miR-3648, miR-4258 and miR-103 | Suppress the transcription factors KLF4 and KLF2 in endothelial cells, consequently enhancing vascular permeability and angiogenesis | Colorectal cancer | |||
miR-203 | Induce the polarization of macrophages to M2-TAMs | Colorectal cancer | |||
miR-135a-5p | Activate LATS2-YAP1/TEAD1-MMP-7 axis | Colorectal cancer | |||
CD44v6/C1QBP complex | Activate hepatic stellate cells and promote liver fibrosis. | Colorectal cancer | |||
Microenvironment | Lipopolysaccharide | Enhance the adhesion of neutrophils and CTCs and increase CTC recruitment to the liver | Lung cancer | ||
IL-22 | Induce aminopeptidase N expression of in endothelial cells | Colorectal cancer | |||
TGF-β | Cause hepatic stellate cells to produce excess fibronectin | Pancreatic ductal adenocarcinoma | |||
Fibronectin | Recruit bone marrow-derived macrophage and neutrophil | Pancreatic ductal adenocarcinoma | |||
Bone | Vicious cycle | OPN, PTHrP, HPSE, PGE2 and cytokines like IL-1, IL-6 | Increase the production of osteoclasts | Breast cancer | |
IGF-1, platelet-derived growth factor (PDGF), and TGF-β | Provide space and fertile soil for tumor growth | Breast cancer | |||
SCUBE2 | Regulate osteoblast differentiation and immunosuppressive niches formation | Breast cancer | |||
Characteristics of CTCs | PDGFR-α | Transform CTCs into a more aggressive phenotype | Breast cancer | ||
SDF-1/CXCR4 | Mediate the adhesion between bone marrow endothelial cells and CTCs | Prostate cancer | |||
TFF3 | Higher tendency to bone | Breast cancer | |||
Lymph node | Characteristics of CTCs | VIM, uPAR and CXCR4 | A more aggressive and malignant phenotype | Cervical and breast cancer | |
FR-positive CTCs | Show a propensity for lymph node metastasis | LUAD | |||
CD24 and CD44 | The markers of metastatic potential | Gastric and breast cancer | |||
KRT-19 | Enhanced organ-specific metastatic activity | Breast cancer | |||
hMAM, Survivin, and hTERT | Enhanced organ-specific metastatic activity | Breast cancer | |||
Bcl-xL | Enhanced organ-specific metastatic activity | Breast cancer | |||
Microenvironment | VEGF-A/C | Activate LN lymphangiogenesis and induce lymphatic network expansion | Breast cancer | ||
CXCL1 and CXCL8 | Recruit neutrophils | Bladder Cancer | |||
VEGF | Induce a Th2-mediated chronic inflammatory milieu | Melanoma | |||
PGE2 and TGF-β | Induce the immunosuppression of dendritic cells | Ovarian tumor | |||
IL-10 and TGF-β | Immunosuppressive cytokines which convert helper T cells to regulatory T cells | Colorectal Cancer |
