title: Interactions of human prostatic epithelial cells with bone marrow endothelium: binding and invasion.
abstract: Prostate cancer shows a propensity to form secondary tumours within the bone marrow. Such tumours are the major cause of mortality in this disease. We have developed an in vitro system to study the binding of prostate epithelial cells to bone marrow endothelium (BME) and stroma (BMS). The metastatic prostate cancer cell line, PC3 (derived from a bone metastasis), was seeded onto confluent layers of BME and its binding characteristics compared to human umbilical vein endothelial cells (HUVEC), lung endothelium (Hs888Lu) and BMS. The PC3 cell line showed significantly increased binding to BME (P< 0.05) compared to endothelium derived from HUVEC and lung or BMS with maximal binding occurring at 1 h. Following pre-incubation with a beta1 integrin antibody PC3 binding to BME was inhibited by 64% (P< 0.001). Antibodies directed against the integrins beta4, alpha2, alpha4, alpha5 and the cellular adhesion molecules P-selectin, CD31, VCAM-1 and sialy Lewis X showed no effect on blocking PC3 binding. Primary prostatic epithelial cells from both malignant (n = 11) and non-malignant tissue (n = 11) also demonstrated equivalent levels of increased adhesion to BME and BMS compared to HUVEC, peaking at 24 h. Further studies examined the invasive ability of prostate epithelial cells in response to bone marrow endothelium using Matrigel invasion chamber assays. In contrast to the previous results, malignant cells showed an increase (1000 fold) in invasive ability, whilst non-malignant prostate epithelia did not respond. We have shown that both malignant and non-malignant prostate epithelial cells can bind at equivalent levels and preferentially to primary human bone marrow endothelium in comparison to controls. However, only malignant prostate epithelia show increased invasive ability in response to BME.
authors.affiliation: CRC Experimental Haematology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester, M20 4BX, UK.
authors.forename: L J
authors.initials: LJ
authors.lastname: Scott
authors.forename: N W
authors.initials: NW
authors.lastname: Clarke
authors.forename: N J
authors.initials: NJ
authors.lastname: George
authors.forename: J H
authors.initials: JH
authors.lastname: Shanks
authors.forename: N G
authors.initials: NG
authors.lastname: Testa
authors.forename: S H
authors.initials: SH
authors.lastname: Lang
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology* / Q000601:surgery; D001854:Bone Marrow Cells / Q000166:cytology*; D002459:Cell Fusion; D002478:Cells, Cultured; D018920:Coculture Techniques; D004727:Endothelium / Q000166:cytology; D004730:Endothelium, Vascular / Q000166:cytology; D004847:Epithelial Cells / Q000166:cytology / Q000473:pathology*; D005347:Fibroblasts / Q000166:cytology / Q000473:pathology; D006801:Humans; D007700:Kinetics; D008168:Lung; D008297:Male; D009361:Neoplasm Invasiveness; D011467:Prostate / Q000166:cytology / Q000473:pathology*; D011470:Prostatic Hyperplasia / Q000473:pathology / Q000601:surgery; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000601:surgery; D017154:Stromal Cells / Q000166:cytology; D014471:Umbilical Veins