Regulation of tumor growth and angiogenesis in colorectal cancer
| Autor: | H.-P. Bruch, Erik Schloericke, J. Nolde, C. deWit, Tilman Laubert |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Oncology
medicine.medical_specialty business.industry Colorectal cancer Angiogenesis medicine.disease medicine.disease_cause Metastasis Vascular endothelial growth factor chemistry.chemical_compound HIF1A chemistry Apoptosis Cell culture Internal medicine Cancer research Medicine Surgery business Carcinogenesis |
| Zdroj: | European Surgery. 44:336-340 |
| ISSN: | 1682-4016 1682-8631 |
| Popis: | Hypoxia in malignant tissues is associated with poor prognosis and treatment options. It is obvious that the grade of malignancy is associated with dedifferentiation of a given tissue. Our aim was to assess the expression of proteins that act as cellular oxygen sensors, which directly regulate the hypoxia-inducible factor 1 (HIF-1) pathway, i.e., prolyl hydroxylase domain proteins (PHD) PHD-1, PHD-2, PHD-3, and its target gene vascular endothelial growth factor (VEGF) in colorectal cancer (CRC). In this study, we cultured a human colon cancer cell line (SW480) and its correspondent lymph-node metastasis cell line (SW620) under normoxic or hypoxic conditions for different time periods. We then measured the HIF-1a expression using Western-Blot, the messenger RNA (mRNA)-expression of the PHDs with real-time polymerase chain reaction (PCR) and the amount of one of the target-genes using an VEGF-ELISA. SW620 shows a clearly elevated HIF-1a expression under normoxic and hypoxic states compared with SW480. Under hypoxic conditions, the amount of VEGF is elevated in both primary and secondary tumor-cell line, but the metastasis-cell line has a significant higher increase. PHD-1 shows no higher expression under hypoxic condition, PHD-2 expression is elevated but only in SW480. PHD-3 levels raised in both of the cell lines, with significant higher rates in SW480. HIF-regulating proteins are highly expressed in CRCs and their metastases. These molecules play an important role in the control of hypoxia-induced genes and may also have a function in the regulation of cellular proliferation and differentiation during tumorigenesis and dedifferentiation of CRCs. Our results emphasize the important role of PHDs not only as an oxygen-sensor, but also as a control-unit for tumor growth, apoptosis, and angiogenesis through HIF-1 pathway. |
| Databáze: | OpenAIRE |
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