lewis-x-antigen and Bone-Neoplasms

Prostate tumor cells preferentially adhere to bone marrow endothelial cells (BMECs) compared with endothelial linings from other tissue microvessels, implicating the importance of BMEC adhesion in the predilection of prostate tumor metastasis to bone. E (endothelial)-selectin, which functions as an initiator of leukocyte adhesion to target tissue endothelium, is constitutively expressed on BMECs, suggesting that prostate tumor cells could use this adhesive mechanism to initiate their migration into bone. In this report, we demonstrate for the first time that human bone-metastatic prostate tumor cells roll on human BMECs under physiological flow conditions. We show that these dynamic adhesive interactions are dependent on the expression of BMEC E-selectin and sialylated glycoconjugates on bone-metastatic prostate tumor cells. We also establish the importance of both glycoprotein(s) and glycosphingolipid structures displaying sialyl Lewis X epitopes as potential E-selectin ligands on bone-metastatic prostate tumor cells. Coexpression of sialylated glycoproteins and glycolipids on bone-metastatic prostate tumor cells triggers robust E-selectin binding activity, which is identical to that observed on human hematopoietic progenitor cells. By Western blot analysis, we identify candidate E-selectin glycoprotein ligand(s); distinct sialyl Lewis X (or HECA-452 antigen)-bearing membrane proteins were resolved at M(r) 130,000 and M(r) 220,000 as well as others ranging from M(r) 100,000 to M(r) 220,000. Immunohistochemical analysis of HECA-452 antigen expression on normal prostate tissue and on low- and high-grade prostate adenocarcinoma shows that HECA-452 antigen expression is directly associated with prostate tumor progression and may indicate acquisition of E-selectin ligand expression. These findings provide novel insight into potential adhesive mechanisms promoting hematogenous dissemination of prostate tumor cells into bone.

Topics: Adenocarcinoma; Antigens, Tumor-Associated, Carbohydrate; Bone Marrow Cells; Bone Neoplasms; Cell Adhesion; Cells, Cultured; Disease Progression; E-Selectin; Endothelium, Vascular; Glycoconjugates; Glycoproteins; Glycosphingolipids; Hematopoietic Stem Cells; Humans; Lewis X Antigen; Ligands; Male; Membrane Proteins; Oligosaccharides; Prostate; Prostatic Neoplasms; Sialyl Lewis X Antigen

report the evidence of regression of multiple metastases following non-myeloablative stem cell transplantation (NST) from an HLA-identical sibling in a case of relapsed fibroblastic osteosarcoma. The course of NST was well tolerated. Full donor chimerism was achieved on day +150 both for CD15+ and CD3+ cells. Complete remission was achieved on day +116. On day +210 the patient relapsed with a scapular metastasis that was unresponsive to four doses of donor lymphocyte infusion (DLIs). To our knowledge, this is the first reported case showing the achievement of complete remission following NST in an osteosarcoma patient.

Topics: Bone Neoplasms; CD3 Complex; Child; Femur; Humans; Immunophenotyping; Lewis X Antigen; Lymphocyte Subsets; Male; Neoplasm Metastasis; Neoplasm Recurrence, Local; Osteosarcoma; Stem Cell Transplantation; Transplantation Chimera

Monoclonal antibodies B1 and B3 react with Lewis(y) and related carbohydrate antigens, which are abundant in many solid tumors. These antibodies, when conjugated to a toxin, have been used to target a variety of cancers. Treatment options for advanced prostate cancer are very limited, and there is a need to develop new therapies. In this study, we have asked whether antibodies B1 and B3 react with metastatic lesions from human prostatic carcinoma.. Indirect streptavidin-biotin peroxidase immunohistochemistry was performed on formalin-fixed specimens from prostate cancer metastases. A total of 6 lymph node metastatic samples from patients who did not receive endocrine treatment and specimens of 14 distant metastases from patients who failed hormonal therapy were obtained.. Of the samples, 6 lymph node and 11 distant metastases stained for B1. In the case of B3 staining, 6 lymph node and 10 distant metastatic lesions were positive. In about half of these metastatic samples, more than 40% of cells were immunoreactive with either antibody. Two metastatic samples stained neither for B1 nor for B3 antibody. In general, B1 staining intensity was stronger in samples in which more than 40% of cells were positive.. Our results suggest that B1 and B3 immunoconjugates could be applied to target a substantial percentage of prostate cancer metastases.

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Biotin; Bone Neoplasms; Humans; Immunoconjugates; Immunohistochemistry; Immunotoxins; In Vitro Techniques; Lewis Blood Group Antigens; Lewis X Antigen; Lymphatic Metastasis; Male; Neoplasm Metastasis; Peroxidase; Prostatic Neoplasms; Streptavidin