Identification of leukocyte E-selectin ligands, P-selectin glycoprotein ligand-1 and E-selectin ligand-1, on human metastatic prostate tumor cells.
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.
Dimitroff
Charles J
CJ
Harvard Skin Disease Research Center, Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts, USA. cdimitroff@rics.bwh.harvard.edu
Descheny
Leyla
L
Trujillo
Natalia
N
Kim
Robert
R
Nguyen
Vuong
V
Huang
Wei
W
Pienta
Kenneth J
KJ
Kutok
Jeffery L
JL
Rubin
Mark A
MA
D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism / Q000556:secondary; D001932:Brain Neoplasms / Q000378:metabolism / Q000556:secondary; D045744:Cell Line, Tumor; D019040:E-Selectin / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D008207:Lymphatic Metastasis; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051379:Mice; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis*; D012795:Sialoglycoproteins
D019040:E-Selectin; D008024:Ligands; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D017468:Receptors, Fibroblast Growth Factor; D012795:Sialoglycoproteins; C086711:cysteine-rich fibroblast growth factor receptor