| Dokumentenart: | Artikel | ||||
|---|---|---|---|---|---|
| Titel eines Journals oder einer Zeitschrift: | Clinical Hemorheology and Microcirculation | ||||
| Verlag: | IOS PRESS | ||||
| Ort der Veröffentlichung: | AMSTERDAM | ||||
| Band: | 70 | ||||
| Nummer des Zeitschriftenheftes oder des Kapitels: | 4 | ||||
| Seitenbereich: | S. 543-551 | ||||
| Datum: | 2019 | ||||
| Institutionen: | Medizin > Lehrstuhl für Unfallchirurgie Medizin > Lehrstuhl für Mund-, Kiefer- und Gesichtschirurgie | ||||
| Identifikationsnummer: |
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| Stichwörter / Keywords: | GROWTH-FACTOR-BB; STROMAL CELLS; TUMOR-GROWTH; CANCER GROWTH; RECRUITMENT; BETA; ANGIOGENESIS; INHIBITION; PERICYTES; Mesenchymal stem cells; migration; breast cancer; PDGF-BB; PI3K pathway | ||||
| Dewey-Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin | ||||
| Status: | Veröffentlicht | ||||
| Begutachtet: | Ja, diese Version wurde begutachtet | ||||
| An der Universität Regensburg entstanden: | Ja | ||||
| Dokumenten-ID: | 47582 |
Web of ScienceZusammenfassung
INTRODUCTION: Mesenchymal stem cells (MSCs) have been described in breast cancer models to migrate towards carcinoma and integrate into tumor associated stroma supporting tumor growth, increasing their metastatic potency and contributing to tumor-angiogenesis. Platelet-derived growth factor (PDGF) isoforms (AA, BB, CC) stimulate growth, survival and motility of MSCs and certain other cell types. ...
Zusammenfassung
INTRODUCTION: Mesenchymal stem cells (MSCs) have been described in breast cancer models to migrate towards carcinoma and integrate into tumor associated stroma supporting tumor growth, increasing their metastatic potency and contributing to tumor-angiogenesis. Platelet-derived growth factor (PDGF) isoforms (AA, BB, CC) stimulate growth, survival and motility of MSCs and certain other cell types. Noteworthy, breast carcinomas are known to express PDGF. We aim to further shed light on i) the relevance of the different PDGF isoforms on adipose tissue derived stem cells (ASCs) migration and ii) the underlying pathway dependent on PDGF stimulation. MATERIALS AND METHODS: Breast cancer cell lines were purchased and ASC's were isolated from murine subcutaneous adipose tissue. The transmigration of ASC' s towards the PDGF-isoforms was assessed by using recombinant human PDGF-AA, PDGF-BB and PDGF-CC in a trans-well culture dish system. Transmigrated ASC's were quantified in 5 randomly selected fields per condition using fluorescence microscopy after calcein-staining. PDGF-BB depended transmigration of ASC' s was verified by downregulation and overexpression of PDGF-BB in breast cancer cell line using lentiviral vectors. In addition, a PI3-kinase inhibitor (LY294002) and a MAP-kinase inhibitor (PD98059) were used to identify the pathway involved in the PDGF-BB mediated migration of ASC's towards tumor. RESULTS: ASC' s transmigration significantly increased towards PDGF AA at 50 ng and only showed further increase by 500 ng which was similar to cell behavior when exposed to PDGF CC. In comparison, PDGF-BB significantly increased ASC's transmigration already at a low level of 5 ng with further significant increase for 20 ng and 40 ng. Cell transmigration was blocked with PDGFR-alpha antibodies but only for PDGF-AA and PDGF-CC whereas PDGFR-beta blockage showed a significant effect on transmigration for PDGF-BB and PDGF-CC but not for PDGF-AA. Neutralizing antibodies in combination with PDGF receptor blockage confirmed findings. In addition, only PI3-kinase inhibitor but not the MEK-1 selective inhibitor caused a significant decrease of transmigration for ASCs towards breast cancer cells. DISCUSSION: The transmigration of ASC's is most significantly enhanced by PDGF-BB via the PI3-kinase pathway. This data support that PI3-kinase is an important key player for MSC migration towards malignancy which need further research to prevent tumor progression in early disease stage.
Metadaten zuletzt geändert: 28 Jul 2021 17:26
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