Expression of early placenta insulin-like growth factor in breast cancer cells provides an autocrine loop that predominantly enhances invasiveness and motility
| Autor: | Buerger H, Nico Dankbar, Matuschek A, Mike W Helms, Simon R, Christian Kersting, D. Kemming, Jean-Michel Bidart, Bartkowiak K, Werner Boecker, Bellet D, B Hinrichs, Dittmar T, J Packeisen, Feldmann U, Sauter G, Burkhard Brandt |
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| Rok vydání: | 2005 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty Receptor ErbB-2 Endocrinology Diabetes and Metabolism medicine.medical_treatment Paget's Disease Mammary Protein Array Analysis Motility Breast Neoplasms Biology Insulin-like growth factor Endocrinology Cell Movement Cell Line Tumor medicine Humans Neoplasm Invasiveness RNA Small Interfering skin and connective tissue diseases Autocrine signalling Protein kinase B Tissue microarray Growth factor Cancer Endothelial Cells medicine.disease Prognosis Immunohistochemistry Autocrine Communication Oncology SKBR3 Culture Media Conditioned Cancer research Intercellular Signaling Peptides and Proteins Female |
| Zdroj: | Endocrine-related cancer. 12(4) |
| ISSN: | 1351-0088 |
| Popis: | Early placenta insulin-like growth factor (EPIL) is expressed by a subpopulation of the Her2-positive SKBR3 breast cancer cell line displaying high motility and transendothelial invasiveness in vitro, as recently shown by our group. As a consequence of this, we established cellular models by generating an EPIL-overexpressing SKBR3 cell line, knocked down EPIL by adding specific small interfering RNA (siRNA) to those cells and produced EPIL-enriched and depleted serum-free culture media. EPIL-expressing cells as well as EPIL-induced SKBR3 cells acquired a high capacity for transendothelial invasiveness. We observed a thin and outspread morphology caused by enhanced formation of lamellipodia, i.e. protrusions in the initial phase of motility. In parallel, Her2-positive MDAHer2 breast cancer cells also showed increased invasiveness when induced by EPIL-conditioned medium. A downstream signaling impact of EPIL could be observed in the form of reduced phosphorylation of Her2, erk1/2 and akt, while phospholipase Cγ1 phophorylation remained unaffected. As an in vivo model for highly motile tumor cells, Paget’s disease of the nipple showed simultaneous EPIL and Her2 expression upon immunohistochemical examination using specific antibodies. Such experimental data have been translated to a clinical setting by using a prognostic tissue microarray established from 603 breast cancer cases. Survival data analysis found a significant association between expression levels of EPIL and 5-year overall survival that was dose dependent: EPIL (negative) 84%, EPIL (moderately positive) 77%, EPIL (strongly positive) 48% (P |
| Databáze: | OpenAIRE |
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