The role of alpha2 beta1 and alpha3 beta1 integrin receptors in the initial anchoring of MDA-MB-231 human breast cancer cells to cortical bone matrix.
Molecular mechanisms involved in the rapid attachment of the human breast cancer cell line MDA-MD-231 to cortical bone matrix were studied. The attachment of MDA-MD-231 cells to cortical bone disks could be blocked by 75% when cells were pretreated with a monoclonal antibody to the beta1-subunit of the integrin family. Monoclonal antibodies against the alpha2, alpha3, and alpha5 integrin subunits inhibited the attachment by 76, 26, and 8 % respectively. Collagenase type I and collagen type I antibody blocked the cell attachment by 45 and 50 % whereas pretreatment of the cells with soluble collagen type I blocked the attachment by 85 %. Our study with a panel of cancer cell lines further showed a close correlation between alpha2 beta1 and alpha3 beta1 integrin receptor expression and the capability to attach to cortical bone. These receptors appear to be the key receptors utilized by cancer cells for the initial attachment to cortical bone, and this could facilitate the localization of alpha2 beta1 and alpha3 beta1 expressing cancer cells to the skeleton.
Department of Biochemistry and Pharmacy, Abo Akademi University, BioCity, Turku, Finland.
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Lundström
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J
Holmbom
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C
Lindqvist
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T
Nordström
D000818:Animals; D001857:Bone Matrix / Q000473:pathology*; D001943:Breast Neoplasms / Q000473:pathology*; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D017364:Collagenases / Q000494:pharmacology; D005260:Female; D006801:Humans; D039201:Integrin alpha3beta1; D016023:Integrins / Q000502:physiology*; D038981:Receptors, Collagen; D014407:Tumor Cells, Cultured
D039201:Integrin alpha3beta1; D016023:Integrins; D038981:Receptors, Collagen; D017364:Collagenases