Drug resistance remains a major obstacle to the successful use of chemotherapeutic drugs for many types of cancers including multiple myeloma. It is becoming increasingly apparent that tumor microenvironment could provide a shelter to malignant plasma cells that allow their survival after initial drug exposure. This study demonstrates alterations in gene expression levels of several extracellular matrix (ECM) components in prednisone, vincristine and melphalan-resistant RPMI-8226 myeloma cells. Resistant RPMI-8226 cells were developed through stepwise selection of cells by increasing concentrations of drugs. Microarray analysis was carried out and genes up-or downregulated more than two-folds were considered as significant. Different types of ECM components were altered in different drug resistant RPMI-8226 sublines. ITGAL and ITGB2 were both overexpressed in vincristine resistant cell line whereas they were both downregulated in prednisone resistant subline. On the other hand, LAMC1 gene was drastically overexpressed in prednisone resistant subline whereas it was downregulated in its melphalan resistant variant. FN1 gene was only upregulated in vincristine resistant cells. However, COL21A1 which is an ECM component of the blood vessel walls, was drastically downregulated in all of the drug resistant RPMI-8226 sublines. ADAM17 gene was upregulated in melphalan resistant subline. This report provides a preliminary in vitro study to the relationship between drug resistance and ECM components in multiple myeloma. Since in vitro developed drug-resistant multiple myeloma sublines do not have similar microenvironment of tumor cells, correlation of ECM proteins with drug resistance requires further analysis. (C) 2012 Elsevier Masson SAS. All rights reserved.