Download Prostate cancer are the most common cancer from

Regulation of metastasis in experimental prostate cancer
Background
Prostate cancer are the most common cancer from in men in Sweden (about 10 000 new cases
per year). Localized prostate cancer can be treated with surgery or radiotherapy, but when the
cancer has spread only hormonal treatment is helpful. Unfortunately, the initially androgendependent tumors overcome androgen ablation and continue to grow as androgen-independent
metastasis, which eventually kill the patient. Prostate cancer preferably establishes metastasis
in the lymph nodes and skeleton.
We have previously established an androgen-independent prostate cancer cell line, LNCaP19, which has increased invasive and angiogenic potential compared to its parental androgendependent cell line. LNCaP-19 is also able to form spontaneous metastasis when implanted
orthotopically in the prostate of immunodeficient mice. Metastases are observed in lymph
nodes, lungs, kidneys and skeleton. We have observed that castration of the mice resulted in
increased tumor growth in the prostate. Therefore, it is interesting to study the effect of
castration on metastatic growth as well as expression of metastasis-related genes in
experimental androgen independent prostate tumors.
Aim
The expression of factors related to metastases and invasivity will be examined in pairs of
primary tumors and metastases from intact and castrated mice. This material is already
collected. The study will focus on vascular endothelial growth factor C (VEGF-C), Ncadherin, and nestin. VEGF-C is a growth factor for lymphatic vessels that are frequently
upregulated in metastasizing prostate cancer. N-cadherin promotes the migration of tumor
cells, and we have preliminary data indicating upregulation of N-cadherin after castration.
Nestin is recently found to be of importance for the migration of tumor cells and have been
found to be upregulated in aggressive cancers.
Work plan
1. Examining the expression of factors related to metastases and invasion in pairs of primary
tumors and metastases with immunohistochemistry and Western blot.
- Vascular endothelial growth factor C (VEGF-C)
- N-cadherin
- Nestin
2. In vitro studies on the androgen regulation of N-cadherin expression in androgen
independent prostate cancer cells, analyzed with real-time PCR.
3. Correlation of the examined factors with micro vessel density and lymphatic vessel density
in primary tumors and metastases.
The research group is located at Lundberg Laboratory for Cancer Research at Sahlgrenska.
The group is run by Prof. Jan-Erik Damber and PhD Karin Welén.
To apply contact:
Karin Welén, PhD
Lundberg Laboratory for Cancer Research
Gula stråket 8, Sahlgrenska
Email: [email protected]
Phone: 031-342 1528