E-/P-selectins and colon carcinoma metastasis: first in vivo evidence for their crucial role in a clinically relevant model of spontaneous metastasis formation in the lung.
BACKGROUND
Interactions of endothelial selectins with tumour cell glycoconjugates have been shown to have a major role in tumour cell dissemination in previous experiments. However, experiments validating this observation were limited in value, as 'metastases' in these experiments were artificially induced by i.v. injection rather than developed spontaneously as in true metastases.


METHODS
Endothelial (E) and platelet (P)-selectin-deficient severe combined immunodeficient (scid) mice were generated and human HT 29 colon cancer cells were subcutaneously inoculated in these mice and in wild-type scid mice. Tumour growth, spontaneous metastasis formation in the lung and adherence of HT29 cells to E- and P-selectin under flow were determined.


RESULTS
The number of metastases decreased by 84% in E- and P-selectin-deficient scid mice, compared with wild-type scid mice. The remaining 16% metastases in the E- and P-selectin-deficient scid mice grew within the pulmonary artery and not in the alveolar septae as they did in wild-type scid mice. Flow experiments indicate that tumour cells roll and tether on an E- and P-selectin matrix similar to leukocytes; however, firm adhesion is mainly mediated in E-selectin.


CONCLUSIONS
Our results indicate that E- and P-selectins have a crucial role in spontaneous metastasis formation. As the human HT 29 colon cancer cells are positive for the lectin Helix pomatia agglutinin (HPA), which identified the metastatic phenotype in earlier clinical studies, these results are of particular clinical relevance.
Köhler
S
S
Institute for Anatomy II: Experimental Morphology, University Cancer Center Hamburg, University Medical Center Hamburg Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
Ullrich
S
S
Richter
U
U
Schumacher
U
U
D000818:Animals; D002448:Cell Adhesion; D003110:Colonic Neoplasms / Q000473:pathology*; D019040:E-Selectin / Q000502:physiology*; D019073:HT29 Cells; D006801:Humans; D037102:Lectins / Q000378:metabolism; D008175:Lung Neoplasms / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009360:Neoplastic Cells, Circulating; D009844:Oligosaccharides / Q000032:analysis; D019007:P-Selectin / Q000032:analysis / Q000502:physiology*; D000080506:Sialyl Lewis X Antigen
D019040:E-Selectin; C038095:Helix lectin; D037102:Lectins; D009844:Oligosaccharides; D019007:P-Selectin; D000080506:Sialyl Lewis X Antigen