The analysis showed that serum levels of ADAM10 and ADAM28 are significantly higher in patients with colorectal cancer and correlate with histopathological grading and with presence of distant metastases.
The results indicated that of the 333 patients with HCC, those who carried ADAM10rs514049 (AC + CC) variants had a higher risk of developing lymph node metastasis (odds ratio [OR] = 5.087, p = 0.027), and those who carried ADAM10rs653765 (GA + AA) variants had a higher risk of developing distant metastasis (OR = 3.346, p = 0.020) and higher levels of α-fetoprotein.
ADAM10 and p75<sup>NTR</sup> ICD also promoted tumor metastasis formation <i>in vivo</i> Together, our findings uncover a previously unknown function for the ADAM10-p75<sup>NTR</sup> ICD-TRAF6-NFκB axis in preventing anoikis and suggest ADAM10 and p75<sup>NTR</sup> ICD as potential cancer therapeutic targets.<b>Significance:</b> These findings identify the ADAM10-p75<sup>NTR</sup> ICD-TRAF6-NFκB signaling axis as a potential candidate for cancer therapy.<i></i>.
Similar results were obtained upon exposure of tumor cells to platelet-releasate and can be attributed to the sheddases ADAM10 and ADAM17 that are detectable on the platelet surface and in releasate following activation and at higher levels on platelets of patients with metastasized lung cancer compared with healthy controls.
These results suggest that proMMP-9, which binds to a receptor complex containing TIMP-1 and ADAM10, is activated by the MT1-MMP/MMP-2 axis, and MMP-9 thus activated stimulates cellular proteolysis and metastasis.
In conclusion, active ADAM10 promotes the carcinogenesis, invasion, metastasis and proliferation of ESCC and controls invasion and metastasis at least in part through the shedding of E-cadherin activity, which makes it a potential biomarker and a useful therapeutic target for ESCC.
Furthermore, analysis of human pancreatic tumor tissue microarrays and lysates showed elevated levels of ADAM10, suggesting that aberrant activation of ADAM10 plays a fundamental role in growth and metastasis of PDACs and inhibiting this pathway might be a viable strategy to combat PDACs.
Mechanistically, miR-144/451 inhibits cancer metastasis by targeting the A disintegrin and metalloproteinase (ADAM) protein family members ADAMTS5 and ADAM10.
There were significant associations between protein levels of ADAM10 and tumour grade, amount of tumour differentiation, tumour size and the presence of metastasis.
In addition, with chromatin immunoprecipitation assay, PAX2 overexpression and PAX2 siRNA we present compelling evidence that PAX2 can regulate ADAM10 expression, a metalloproteinase known to play important roles in melanoma metastasis.
Immunohistochemical analysis on tissue microarrays indicated that ADAM10 expression was significantly elevated in melanoma metastasis compared with primary melanomas.
Additionally, silencing of ADAM 10 resulted in inhibition of cell growth and invasion in vitro as well as inhibition of cancer metastasis in an experimental murine model of lung metastases in vivo.
ADAM10 overexpression in colon cancer cells displaying endogenous L1-CAM enhanced L1-CAM cleavage and induced liver metastasis, and ADAM10 also enhanced metastasis in colon cancer cells stably transfected with L1-CAM.