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. 2012 Sep 1;6(5):424–432. doi: 10.4161/cam.21559

Table 2. Summary of in vivo metastasis data, targeting the adhesion molecules described in Table �1.

Adhesion
molecule
In vivo model Metastasis phenotype
FAK
Intravenous injection
of FAK−/− tumor cells82
Failed to form lung tumors; cells retained in the lung capillary bed were rounded and lacked membrane extensions into the vessel
Activated ErbB2 mammary tumor model with epithelial-specific FAK deletion69
Metastatic lung tumors all negative for cells with homozygous deletion of FAK
Mammary epithelium-specific deletion of FAK in MMTV-PyVmT Mouse Tumor Model70
Metastatic lung tumors all negative for cells with homozygous deletion of FAK
Mammary epithelium-specific deletion of FAK in MMTV-PyVmT Mouse Tumor Model71
Reduced lung tumor metastases
Orthotopic injection of pancreatic cancer cells treated with FAK siRNA73
Prevented formation of liver metastases
p130Cas
Mammary tumor model—injection of cells expressing inducible p130Cas shRNA77
Inhibits lung colonization
Athymic nude mice injected sub-cutaneously with p130Cas−/− fibroblasts transformed with oncogenic Src and expressing p130Cas78
Exogenous p130Cas expression increased formation of metastatic lung tumors after surgical removal of primary tumors; authors comment that “the capacity of the cells to invade through matrigel was strongly correlated with their capacity to invade and metastasize in vivo”
Vinculin
Exogenous vinculin expression in highly metastatic rat adenocarcinoma injected into foot pad80
Highest levels of vinculin expression suppressed formation of lung metastases, low to moderate expressors formed tumors in lymph nodes close to injection site but failed to form lung metastases
NEDD9
Mammary epithelium-specific deletion of NEDD9 in MMTV-PyVmT Mouse Tumor Model67
Trend to fewer lung metastases
Tail vein injection of NEDD9-null primary tumors8
Tumors formed of null-cell lines exhibited increased aggressiveness, with all injected mice generating secondary tumors
Talin
Tail vein injections of prostate cancer cell lines treated with talin shRNA84
Reduced numbers of metastatic lung lesions
αvβ3
Orthotopic injection into mammary fat pad with mammary carcinoma cell line expressing exogenous β376
Drove unique formation of bone metastases; authors show increased haptotactic and chemotactic response to bone-matrix proteins and soluble factors
MDA-MB-435 breast cancer cells expressing constitutively active αvβ3 injected into mouse tail vein81
Enhanced lung colonization
Intravenous injection of metastatic αvβ3 negative melanoma cells expressing exogenous β391
Re-expression of β3 in metastatic, β3 negative lines reduced lung colonization
β1 integrin
Conditional deletion of β1 integrin from mammary epithelia, crossed with MMTV/activated erbB272
Significantly reduced formation of lung metastases
Orthotopic injection of pancreatic cancer cells treated with β1 integrin siRNA74
Absence of any metastatic tumors; controls treated with α2 or α3 integrin subunit siRNA displayed metastatic tumors
Conditional deletion of β1 integrin from pancreatic β cells crossed with Rip1Tag2 mice68
Loss of β1 expression induced increased tumor cell emboli in the lymphatic vasculature but no metastasis formation; similarly, tail vein injections of β tumor cells lacking β1 integrin expression did not form metastases
Ras-myc transformed β1 null ES cells injected sub-cutaneously79
Reduced numbers and size of metastatic foci in the lung
α5β1 integrin HT-29 colon cancer cells expressing exogenous α5 integrin injected intravenously85
Significantly reduced lung and extrapulmonary metastases
Lewis Lung Carcinoma cells expressing α5 shRNA injected into tail vein83 Fewer lung tumors