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Identification of Leukocyte E-Selectin Ligands, P-Selectin Glycoprotein Ligand-1 and E-Selectin Ligand-1, on Human Metastatic Prostate Tumor Cells

¹ Harvard Skin Disease Research Center, Department of Dermatology, and ² Department of Pathology, Brigham and Women's Hospital; ³ Harvard Medical School, Boston, Massachusetts; and ⁴ Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan

Requests for reprints: Charles J. Dimitroff, Harvard Institutes of Medicine, Room 650, 77 Avenue Louis Pasteur, Boston, MA 02115. Phone: 617-525-5693; Fax: 617-525-5571; E-mail: cdimitroff{at}rics.bwh.harvard.edu.

Prostate tumor cells, which characteristically metastasize to bone, initiate binding interactions with bone marrow endothelium under blood flow conditions through binding interactions with E-selectin. We hypothesized that E-selectin ligands on prostate tumor cells are directly associated with bone-metastatic potential. In this report, we elucidate the identity of E-selectin ligands on human metastatic prostate tumor cells and examine their association with prostate tumor progression and metastasis in vivo. To our surprise, we found that the E-selectin-binding form of P-selectin glycoprotein ligand-1 (PSGL-1) is expressed on the human bone-metastatic prostate tumor MDA PCa 2b cell line. Interestingly, we also found that human prostate tumor cells derived from bone, lymph node, and brain metastases expressed another leukocyte E-selectin ligand, E-selectin ligand-1 (ESL-1). Immunohistochemical analysis of PSGL-1 and ESL-1 in normal prostate tissue and in localized and metastatic prostate tumors revealed that ESL-1 was principally localized to intracellular cell membrane and expressed on all normal and malignant prostate tissue, whereas PSGL-1 was notably detected on the surfaces of bone-metastatic prostate tumor cells. These findings implicate a functional role of PSGL-1 in the bone tropism of prostate tumor cells and establish a new perspective into the molecular mechanism of human prostate tumor metastasis.