Title | Identification of leukocyte E-selectin ligands, P-selectin glycoprotein ligand-1 and E-selectin ligand-1, on human metastatic prostate tumor cells. |
Publication Type | Journal Article |
Year of Publication | 2005 |
Authors | Dimitroff CJ, Descheny L, Trujillo N, Kim R, Nguyen V, Huang W, Pienta KJ, Kutok JL, Rubin MA |
Journal | Cancer Res |
Volume | 65 |
Issue | 13 |
Pagination | 5750-60 |
Date Published | 2005 Jul 1 |
ISSN | 0008-5472 |
Keywords | Animals, Bone Neoplasms, Brain Neoplasms, Cell Line, Tumor, E-Selectin, Humans, Immunohistochemistry, Ligands, Lymphatic Metastasis, Male, Membrane Glycoproteins, Mice, Prostatic Neoplasms, Receptors, Fibroblast Growth Factor, Sialoglycoproteins |
Abstract | 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. |
DOI | 10.1158/0008-5472.CAN-04-4653 |
Alternate Journal | Cancer Res. |
PubMed ID | 15994950 |
PubMed Central ID | PMC1472661 |
Grant List | 1R21 CA102913-02 / CA / NCI NIH HHS / United States 1R21 CA104828-01 / CA / NCI NIH HHS / United States 5P30 AR042689 / AR / NIAMS NIH HHS / United States CA06516-37 / CA / NCI NIH HHS / United States CA69568 / CA / NCI NIH HHS / United States R21 CA102913 / CA / NCI NIH HHS / United States R21 CA104828 / CA / NCI NIH HHS / United States |