Aberrant Presentation of HPA-Reactive Carbohydrates Implies Selectin-Independent Metastasis Formation in Human Prostate Cancer

Abstract

Purpose: To investigate the impact of prostate cancer cell surface glycosylation as part of the tumor cellendothelial cell interaction in prostate cancer metastasis.Experimental Design: Glycosyltransferase expression was profiled in metastasis-derived prostate cancer cell lines and compared with primary epithelium. Prostate cancer cells were examined for HPA-and selectinbinding and adhesion to endothelium. Spontaneous metastasis xenograft models were established to test the lectin HPA-binding sites as a marker of metastatic competence and to evaluate E-selectin-binding sites in vivo. The importance of selectins for metastasis formation was analyzed using Seleclinical relevance of HPA-and E-selectin-binding sites in prostate cancer was determined.Results: Glycosyltransferases involved in the synthesis of common HPA-binding sites are downregulated in prostate cancer cells. An absence of HPA-reactive carbohydrates specifically indicates spontaneous metastatic spread of prostate cancer xenografts in vivo and a poor prognosis of patients with prostate cancer. HPA-binding sites decrease in lymph node metastases compared with corresponding primary tumors. Common selectin ligands are absent on prostate cancer cells, which do not adhere to recombinant selectins or endothelium under shear stress in vitro. Spontaneous metastasis formation is largely independent of selectins in vivo. E-selectin-binding sites are detectable in only 2% of patients with prostate cancer without prognostic significance.Conclusion: Prostate cancer is characterized by an inverse functional and prognostic importance of HPAbinding sites compared with other adenocarcinomas. Accordingly, this study surprisingly shows that the selectin-selectin ligand axis, which is essential for extravasation and thus metastasis formation in several malignancies, can be circumvented in prostate cancer.

The marine triterpene glycoside frondoside A exhibits activity in vitro and in vivo in prostate cancer

“…Human cancer cells were recognized by their characteristically large, basophilic, and polymorphic nuclei, which were clearly distinguishable from the smaller nuclei of mouse cells. The analysis was performed by two investigators blinded to the treatment, with a particular focus on the distinction of intrastromal micrometastases and intravascular tumor cells, which were analyzed as described before …”

“…The analysis was performed by two investigators blinded to the treatment, with a particular focus on the distinction of intrastromal micrometastases and intravascular tumor cells, which were analyzed as described before. 29…”

Modeling Spontaneous Bone Metastasis Formation of Solid Human Tumor Xenografts in Mice

“…At this initial stage, the experimental setup was to inject tumor cells from different human cancer cell lines s.c. into immunodeficient mice and to terminate the experiment when the s.c. tumor reached around 1.5 cm 3 . By using quantitative PCR for human-specific DNA sequences (Alu-PCR), we indeed observed variable metastatic cell loads in the murine BM depending on the respective cell line [9,10,18,20]. This methodology was used to test whether MDA-MB-231(SA) cells have an increased bone-metastatic potential compared to wild-type MDA-MB-231 cells.…”

“…In our initial experiments, we injected human cancer cells of different cell lines (PC-3, VCaP, DU4475) s.c. into immunodeficient mice (xenograft) and sacrificed the mice as soon as the s.c. xenograft tumors were about 1.5 cm 3 . At this stage, we determined the metastatic cell load in the BM by means of human-specific genome sequences quantified by Alu-PCR ( Figure 1B) and detected rather low cell numbers in the BM [9,10]. This approach was also used in an additional model to compare the spontaneous BM metastasis capacity of wild-type MDA-MB-231 breast cancer cells and the "bone-seeking" subline MDA-MB-231(SA) [11,12].…”

Development and Applications of Lectins as Biological Tools in Biomedical Research

“…HPA binding is also associated with the metastasis of other cancers, such as lung cancer, melanoma, prostate cancer, and colon carcinoma . About 90% of 96 patients with metastatic adenocarcinoma of the lung expressed HPA‐binding glycoproteins .…”