Selectins promote tumor metastasis.
Cancer metastasis is facilitated by cell-cell interactions between cancer cells and endothelial cells in distant tissues. In addition, cancer cell interactions with platelets and leukocytes contribute to cancer cell adhesion, extravasation, and the establishment of metastatic lesions. Selectins are carbohydrate-binding molecules that bind to sialylated, fucosylated glycan structures, and are found on endothelial cells, platelets and leukocytes. There are three members of the selectin family: P-selectin expressed on activated platelets and endothelial cells, L-selectin present on leukocytes and E-selectin expressed on activated endothelial cells. Besides the accepted roles of selectins in physiological processes, such as inflammation, immune response and hemostasis, there is accumulating evidence for the potential of selectins to contribute to a number of pathophysiological processes, including cancer metastasis. Cancer cell interactions with selectins are possible due to a frequent presence of carbohydrate determinants--selectin ligands on the cell surface of tumor cells from various type of cancer. The degree of selectin ligand expression by cancer cells is well correlated with metastasis and poor prognosis for cancer patients. Initial adhesion events of cancer cells facilitated by selectins result in activation of integrins, release of chemokines and are possibly associated with the formation of permissive metastatic microenvironment. While E-selectin has been evaluated as one of the initiating adhesion events during metastasis, it is becoming apparent that P-selectin and L-selectin-mediated interactions significantly contribute to this process as well. In this review we discuss the current evidence for selectins as potential facilitators of metastasis.
Läubli
Heinz
H
Institute of Physiology, University of Zürich, Zürich Center for Integrative Human Physiology, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
Borsig
Lubor
L
D000818:Animals; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology; D018450:Disease Progression; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D019087:Selectins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D055153:Stem Cell Niche / Q000378:metabolism / Q000473:pathology
D008024:Ligands; D019087:Selectins