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A Rapid, Scalable Method for the Isolation, Functional Study, and Analysis of Cell-derived Extracellular Matrix
Published on: January 4, 2017
Differential gene expression analysis related to extracellular matrix components in drug-resistant RPMI-8226 cell
Pelin Mutlu1, Ali Ugur Ural, Ufuk Gündüz
1Middle East Technical University, Central Laboratory, Molecular Biology and Biotechnology R&D Center, Ankara, Turkey. pelinkaya78@yahoo.com
Abstract:
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.
Insights
Drug resistance in multiple myeloma is linked to changes in extracellular matrix (ECM) genes. This study reveals altered ECM gene expression in drug-resistant myeloma cells, highlighting potential therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Drug resistance is a significant challenge in multiple myeloma treatment.
- The tumor microenvironment may protect cancer cells from chemotherapy.
- Extracellular matrix (ECM) components are implicated in cancer progression and drug resistance.
Purpose of the Study:
- To investigate alterations in ECM gene expression in drug-resistant multiple myeloma cell lines.
- To identify specific ECM genes associated with resistance to prednisone, vincristine, and melphalan.
Main Methods:
- Development of drug-resistant RPMI-8226 multiple myeloma cell lines through stepwise drug selection.
- Microarray analysis to assess gene expression levels.
- Identification of genes with greater than two-fold up- or down-regulation.
Main Results:
- Significant alterations in ECM gene expression were observed in drug-resistant sublines.
- ITGAL and ITGB2 showed differential expression in vincristine- and prednisone-resistant cells.
- LAMC1 was overexpressed in prednisone-resistant cells but downregulated in melphalan-resistant cells.
- FN1 was upregulated in vincristine-resistant cells.
- COL21A1 was downregulated across all resistant sublines.
- ADAM17 was upregulated in melphalan-resistant cells.
Conclusions:
- This in vitro study suggests a relationship between ECM component alterations and drug resistance in multiple myeloma.
- Further in vivo studies are needed to confirm the role of ECM proteins in the tumor microenvironment and drug resistance.
