title: Viable circulating metastatic cells produced in orthotopic but not ectopic prostate cancer models.
abstract: Elucidation of the mechanisms of hormone-independent metastatic prostate cancer remains a significant and highly relevant challenge. We report here that hormone-refractory human prostate carcinoma growing orthotopically efficiently deliver viable metastatic cells in the host circulation. This is in contrast to the ectopic tumors of the same lineage, which do not deliver live cells into the circulation. To investigate the malignant potential of viable circulating carcinoma cells, we developed a novel dual-color orthotopic coimplantation model of human prostate cancer metastasis in nude mice. This model is comprised of coinjection of an equivalent mixture of isolated and cultured circulating green fluorescent protein-expressing clones and parental red fluorescent protein-expressing human prostate carcinoma cells. In the dual-color model, the selected green fluorescent protein-labeled viable circulating cells have an increased metastatic propensity relative to the red fluorescent protein-labeled parental cells. The identification and isolation of highly malignant viable circulating human prostate carcinoma cells from orthotopic but not ectopic models will enable important new insights into the metastatic process including the role of the tumor microenvironment.
authors.affiliation: Sidney Kimmel Cancer Center, San Diego, California 92121, USA.
authors.forename: Anna B
authors.initials: AB
authors.lastname: Glinskii
authors.forename: Brian A
authors.initials: BA
authors.lastname: Smith
authors.forename: Ping
authors.initials: P
authors.lastname: Jiang
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Li
authors.forename: Meng
authors.initials: M
authors.lastname: Yang
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
authors.forename: Gennadi V
authors.initials: GV
authors.lastname: Glinsky
mesh_terms: D000818:Animals; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology*; D014183:Transplantation, Heterologous