Effect of Hyaluronan and Hyaluronidase on Tumour
Growth and Metastasis
The role of hyaluronan,
hyaluronan receptors and hyaluronidase in tumour cell proliferation,
invasion and metastasis is still a matter of debate. For reviews see,
e. g.:
In a first approach, human
melanoma (SK-MEL-3) and colon carcinoma cells (HT-29) were transfected
with either hyaluronan synthase (DG42) or hyaluronidase (PH20) encoding
genes. Comparing tumorigenicity, growth and metastatic potential of the
HT-29 transfectants with the corresponding wild type cells in nude mice
revealed that both, overexpression of hyaluronan synthase and
hyaluronidase, impaired the tumour cells. However, the PH20 was growing
faster than the DG42 variant. After inoculation of the tumour cells at
low concentrations (105 cells/animal) the DG42
phenotype became non-tumourigenic.
In a second approach, HT-29
cells were genetically modified to stably co-express human Hyal-1 and
the red fluorescent protein Dsred2 as a reporter gene for detection
of metastases by optical in vivo imaging, using an orthotopic
tumor model in nude mice. This visualization technique enabled the
detection of metastases at distant sites such as liver and lung. Hyal-1
overexpression seems to facilitate the metastasis of orthotopic HT-29
tumours.
As the results can not be
unequivocally interpreted without further experiments using selective
inhibitors of hyaluronidase as pharmacological tools we started a
medicinal chemistry project for the development of such
compounds (cf. hyaluronidase
inhibitors).
Cooperation with:
- Prof.
Dr. G. Kreil (Austrian Academy of Sciences, Department of
Molecular Biology, Salzburg, Austria)
Doctoral Theses:
- M. Oettl, Biochemische Charakterisierung
boviner testikulärer Hyaluronidase und Untersuchungen zum
Einfluß von Hyaluronidase und Hyaluronsäure auf das
Wachstum von Tumoren, Regensburg 2000.
- P. Jarzyna, Preclinical investigations on the
effect of the human hyaluronidase Hyal-1 on growth and metastasis of
human colon carcinoma, Regensburg 2007
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