MDR-1-overexpression in HT 29 colon cancer cells grown in SCID mice
| Autor: | Nina Nehmann, Elizabeth C. Adam, Brigitte Schlegelberger, Marcel J. Flens, Doris Steinemann, Dhia Mukthar, Hans-Peter Horny, Itzchak Slotki, Udo Schumacher |
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| Přispěvatelé: | Pathology, CCA - Disease profiling |
| Rok vydání: | 2012 |
| Předmět: |
Male
Pathology medicine.medical_specialty ATP Binding Cassette Transporter Subfamily B Histology Transplantation Heterologous Mice SCID Biology Mice HT29 Cells Cancer stem cell Tumor Cells Cultured medicine Animals Humans Cytotoxic T cell ATP Binding Cassette Transporter Subfamily B Member 1 Cell Proliferation Mice Inbred BALB C Signet ring cell Cell growth Cell adhesion molecule Neoplasms Experimental Cell Biology General Medicine Immunohistochemistry Mice Inbred C57BL Cell culture Cancer research Female Stem cell Neoplasm Transplantation |
| Zdroj: | Schumacher, U, Nehmann, N, Adam, E, Mukthar, D, Slotki, I N, Horny, H P, Flens, M J, Schlegelberger, B & Steinemann, D 2012, ' MDR-1-overexpression in HT 29 colon cancer cells grown in SCID mice ', Acta histochemica, vol. 114, no. 6, pp. 594-602 . https://doi.org/10.1016/j.acthis.2011.11.004 Acta histochemica, 114(6), 594-602. Urban und Fischer Verlag Jena |
| ISSN: | 0065-1281 |
| Popis: | The multidrug-resistance 1 (MDR-1) P-glycoprotein (Pgp) is a transmembrane transporter system, which actively pumps cytotoxic drugs out of the cell. MDR-1 acquired in vitro differs from MDR-1 acquired in vivo, but has important consequences on the cellular phenotype and metastatic behavior. Here we report that the human colonic cancer cell line HT29 (MDR-1 negative) is more malignant than its MDR-1 overexpressing variant (HT29 MDR-1 positive). HT29 MDR-1 negative cells produce undifferentiated signet ring carcinomas when implanted subcutaneously into SCID mice, while HT29 MDR-1 positive cells form tumors with tubular structures, but without signet ring cells. Immunohistochemical proliferation marker analysis revealed that the MDR-1 positive cells proliferate much more slowly than the MDR-1 negative cells. MDR-1 overexpression results in a less differentiated phenotype at the cellular level (absence of mucin producing cells) but in a more differentiated phenotype at the tissue level (tubule formation). In addition, lectin binding patterns including that of Helix pomatia agglutinin (HPA), an indicator of metastatic potential, differed between the two cell lines. HT29 MDR-1 positive cells had less HPA binding sites than HT29 MDR-1 negative counterparts and metastasized less frequently in SCID mice. As slow proliferation, low degree of differentiation and multidrug-resistance is a hallmark of cancer stem cells and all were present in MDR-1 positive tumors, it is attractive to speculate that they represent a stem cell rich tumor. As shown by global gene expression analyses, genes involved, e.g. in cell adhesion, glycosylation and signal transduction, were deregulated in MDR-1 positive tumors compared to MDR-negative tumors. Overexpression of E-cadherin and carcinoembryonic antigen-related cell adhesion molecules 1 (CEACAM1) may provide clues to the mechanisms responsible for the reduced metastatic potential of MDR-1 overexpressing tumors. Since drug treatment shifted the cells towards a less metastatic phenotype in this in vivo model, it seems conceivable to achieve this using drug treatment also in a clinical situation. |
| Databáze: | OpenAIRE |
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