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 |