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European Surgery

Erschienen in:

01.10.2012 | Original Scientific Paper

Regulation of tumor growth and angiogenesis in colorectal cancer

verfasst von: Dr. J. Nolde, Prof. Dr. C. deWit, Dr. E. Schloericke, Prof. Dr. H.-P. Bruch, Dr. T. Laubert

Erschienen in: European Surgery | Ausgabe 5/2012

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Summary

Background

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).

Methods

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.

Results

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.

Conclusions

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.

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Titel: Regulation of tumor growth and angiogenesis in colorectal cancer
verfasst von: Dr. J. Nolde
Prof. Dr. C. deWit
Dr. E. Schloericke
Prof. Dr. H.-P. Bruch
Dr. T. Laubert
Publikationsdatum: 01.10.2012
Verlag: Springer Vienna
Erschienen in: European Surgery / Ausgabe 5/2012
Print ISSN: 1682-8631
Elektronische ISSN: 1682-4016
DOI: https://doi.org/10.1007/s10353-012-0160-1

Springer Medizin Österreich

Summary

Background

Methods

Results

Conclusions

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