High αv Integrin Level of Cancer Cells Is Associated with Development of Brain Metastasis in Athymic Rats
Yingjen Jeffrey Wua, Michael A. Pagelb, Leslie L. Muldoona c, Rongwei F. Fud e, Edward A. Neuweltb f g
- aDepartment of Neurology, Oregon Health & Sciences University, Portland, OR, U.S.A
- bVeterans Administration Medical Center, Portland, OR, U.S.A
- cDepartment of Cell, Developmental & Cancer Biology, Oregon Health & Sciences University, Portland, OR, U.S.A
- dDepartment of Emergency Medicine, Oregon Health & Sciences University, Portland, OR, U.S.A
- eSchool of Public Health, Oregon Health & Sciences University, Portland, OR, U.S.A
- fDepartment of Neurology, Oregon Health & Sciences University, Portland, OR, U.S.A. neuwelte@ohsu.edu
- gDepartment of Neurosurgery, Oregon Health & Sciences University, Portland, OR, U.S.A
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Abstract
BACKGROUND/AIM: Brain metastases commonly occur in patients with malignant skin, lung and breast cancers resulting in high morbidity and poor prognosis. Integrins containing an αv subunit are cell adhesion proteins that contribute to cancer cell migration and cancer progression. We hypothesized that high expression of αv integrin cell adhesion protein promoted metastatic phenotypes in cancer cells. MATERIALS AND METHODS: Cancer cells from different origins were used and studied regarding their metastatic ability and intetumumab, anti-αv integrin mAb, sensitivity using in vitro cell migration assay and in vivo brain metastases animal models. RESULTS: The number of brain metastases and the rate of occurrence were positively correlated with cancer cell αv integrin levels. High αv integrin-expressing cancer cells showed significantly faster cell migration rate in vitro than low αv integrin-expressing cells. Intetumumab significantly inhibited cancer cell migration in vitro regardless of αv integrin expression level. Overexpression of αv integrin in cancer cells with low αv integrin level accelerated cell migration in vitro and increased the occurrence of brain metastases in vivo. CONCLUSION: αv integrin promotes brain metastases in cancer cells and may mediate early steps in the metastatic cascade, such as adhesion to brain vasculature. Targeting αv integrin with intetumumab could provide clinical benefit in treating cancer patients who develop metastases.
TL;DROverexpression of αv integrin in cancer cells with low αv integrin level accelerated cell migration in vitro and increased the occurrence of brain metastases in vivo, which may mediate early steps in the metastatic cascade, such as adhesion to brain vasculature. (Semantic Scholar)