Characterization of hybrid cells derived from spontaneous fusion events between breast epithelial cells exhibiting stem-like characteristics and breast cancer cells.
Several data of the past years clearly indicated that the fusion of tumor cells and tumor cells or tumor cells and normal cells can give rise to hybrids cells exhibited novel properties such as an increased malignancy, drug resistance, or resistance to apoptosis. In the present study we characterized hybrid cells derived from spontaneous fusion events between the breast epithelial cell line M13SV1-EGFP-Neo and two breast cancer cell lines: HS578T-Hyg and MDA-MB-435-Hyg. Short-tandem-repeat analysis revealed an overlap of parental alleles in all hybrid cells indicating that hybrid cells originated from real cell fusion events. RealTime-PCR-array gene expression data provided evidence that each hybrid cell clone exhibited a unique gene expression pattern, resulting in a specific resistance of hybrid clones towards chemotherapeutic drugs, such as doxorubicin and paclitaxel, as well as a specific migratory behavior of hybrid clones towards EGF. For instance, M13MDA435-4 hybrids showed a marked resistance towards etoposide, doxorubicin and paclitaxel, whereas hybrid clones M13MDA-435-1 and -2 were only resistant towards etoposide. Likewise, all investigated M13MDA435 hybrids responded to EGF with an increased migratory activity, whereas the migration of parental MDA-MB-435-Hyg cells was blocked by EGF, suggesting that M13MDA435 hybrids may have acquired a new motility pathway. Similar findings have been obtained for M13HS hybrids. We conclude from our data that they further support the hypothesis that cell fusion could give rise to drug resistant and migratory active tumor (hybrid) cells in cancer.
Dittmar
Thomas
T
Institute of Immunology, Zentrum für Biomedizinische Ausbildung und Forschung an der UWH (ZBAF), Witten/Herdecke University, Stockumer Str. 10, 58448 Witten, Germany. thomas.dittmar@uni-wh.de
Schwitalla
Sarah
S
Seidel
Jeanette
J
Haverkampf
Sonja
S
Reith
Georg
G
Meyer-Staeckling
Sönke
S
Brandt
Burkhard H
BH
Niggemann
Bernd
B
Zänker
Kurt S
KS
D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D002459:Cell Fusion; D002465:Cell Movement; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D004847:Epithelial Cells / Q000473:pathology*; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D005472:Fluorouracil / Q000627:therapeutic use; D020869:Gene Expression Profiling; D006801:Humans; D006822:Hybrid Cells / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D005047:Etoposide; D017239:Paclitaxel; D005472:Fluorouracil