Preferential adhesion of prostate cancer cells to bone is mediated by binding to bone marrow endothelial cells as compared to extracellular matrix components in vitro.
We have demonstrated previously that the preferential adhesion of prostate cancer cells to human bone marrow endothelial (HBME) cells may contribute to their preferential metastasis to bone. Although a subject of debate, it has been postulated that the endothelial cells of the bone marrow are fenestrated. It is unknown therefore whether prostate cancer cells adhere preferentially to the extracellular matrix (ECM) or the endothelial cells. It has also been demonstrated in other organ systems that the types of cell adhesion molecules on the surface of endothelial cells lining the organ microvasculature are determined, in part, by the ECM of the organ. We investigated how prostate cancer cell adhesion to HBME cells is affected by growing HBME cells on selected organ-derived ECM proteins in vitro. Growth of HBME cells and immortalized human aortic endothelial cells on bone, kidney, and placenta ECM proteins significantly increased their ability to bind PC-3 cells. This increased adhesion was not dose dependent and was not demonstrated with human dermal microvascular endothelial cells. Scanning electron microscopic analysis demonstrated that prostate cancer cells adhered directly to the endothelial cells and not to the underlying substrata. These results suggest that unidentified cell adhesion molecules are expressed or up-regulated on the apical surfaces of human aortic endothelial cells and HBME cells grown on bone, kidney, and placenta ECMs. These results also strongly demonstrate that the adhesion of prostate cancer cells to bone may be initiated by direct binding to endothelial cells rather than direct binding to exposed ECM components.
Cooper
C R
CR
Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, Ann Arbor 48109, USA. cacooper@umich.edu
McLean
L
L
Walsh
M
M
Taylor
J
J
Hayasaka
S
S
Bhatia
J
J
Pienta
K J
KJ
D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism / Q000648:ultrastructure; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000166:cytology* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000378:metabolism* / Q000648:ultrastructure; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D008297:Male; D008833:Microcirculation; D008855:Microscopy, Electron, Scanning; D008954:Models, Biological; D010920:Placenta / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D015815:Cell Adhesion Molecules; D005353:Fibronectins; D007797:Laminin; D014168:Transferrin; D003094:Collagen