BACKGROUND: Metastatic prostate cancer is an incurable disease. During the development of this disease, prostate cancer cells enter the bloodstream as single cells or clusters of cells. Prostate fibroblasts, a cancer-promoting cell type in the prostate cancer microenvironment, could in theory incorporate into these migrating cell clusters or follow cancer cells into the bloodstream through holes in the tumor vasculature. Based on this idea, we hypothesized that fibroblast-like cells, defined here as cytokeratin 8/18/19(-) /DAPI(+) /CD45(-) /vimentin(+) cells, are present in the blood of men with metastatic prostate cancer. METHODS: Veridex's CellSearch® system was used to immunomagnetically capture EpCAM(+) cells and clusters of cells heterogeneous for EpCAM expression from the blood of men with metastatic prostate cancer, localized cancer, and no known cancer, and immunostain them for the presence of cytokeratins 8/18/19, a nucleus, CD45, and vimentin. Fibroblast-like cells were then quantified. RESULTS: Fibroblast-like cells were present in 58.3% of men with metastatic prostate cancer but not in any men with localized prostate cancer or no known cancer. The presence of these cells correlated with certain known indicators of poor prognosis: ≥ 5 circulating tumor cells, defined here as cytokeratin 8/18/19(+) /DAPI(+) /CD45(-) cells, per 7.5 ml of blood, and a relatively high serum prostate-specific antigen level of ≥ 20 ng/ml. CONCLUSIONS: The presence of fibroblast-like cells in the blood may provide prognostic information as well as information about the biology of metastatic prostate cancer.
BACKGROUND:Metastatic prostate cancer is an incurable disease. During the development of this disease, prostate cancer cells enter the bloodstream as single cells or clusters of cells. Prostate fibroblasts, a cancer-promoting cell type in the prostate cancer microenvironment, could in theory incorporate into these migrating cell clusters or follow cancer cells into the bloodstream through holes in the tumor vasculature. Based on this idea, we hypothesized that fibroblast-like cells, defined here as cytokeratin 8/18/19(-) /DAPI(+) /CD45(-) /vimentin(+) cells, are present in the blood of men with metastatic prostate cancer. METHODS: Veridex's CellSearch® system was used to immunomagnetically capture EpCAM(+) cells and clusters of cells heterogeneous for EpCAM expression from the blood of men with metastatic prostate cancer, localized cancer, and no known cancer, and immunostain them for the presence of cytokeratins 8/18/19, a nucleus, CD45, and vimentin. Fibroblast-like cells were then quantified. RESULTS: Fibroblast-like cells were present in 58.3% of men with metastatic prostate cancer but not in any men with localized prostate cancer or no known cancer. The presence of these cells correlated with certain known indicators of poor prognosis: ≥ 5 circulating tumor cells, defined here as cytokeratin 8/18/19(+) /DAPI(+) /CD45(-) cells, per 7.5 ml of blood, and a relatively high serum prostate-specific antigen level of ≥ 20 ng/ml. CONCLUSIONS: The presence of fibroblast-like cells in the blood may provide prognostic information as well as information about the biology of metastatic prostate cancer.
Authors: Andrew J Armstrong; Matthew S Marengo; Sebastian Oltean; Gabor Kemeny; Rhonda L Bitting; James D Turnbull; Christina I Herold; Paul K Marcom; Daniel J George; Mariano A Garcia-Blanco Journal: Mol Cancer Res Date: 2011-06-10 Impact factor: 5.852
Authors: Shannon L Stott; Chia-Hsien Hsu; Dina I Tsukrov; Min Yu; David T Miyamoto; Belinda A Waltman; S Michael Rothenberg; Ajay M Shah; Malgorzata E Smas; George K Korir; Frederick P Floyd; Anna J Gilman; Jenna B Lord; Daniel Winokur; Simeon Springer; Daniel Irimia; Sunitha Nagrath; Lecia V Sequist; Richard J Lee; Kurt J Isselbacher; Shyamala Maheswaran; Daniel A Haber; Mehmet Toner Journal: Proc Natl Acad Sci U S A Date: 2010-10-07 Impact factor: 11.205
Authors: Sunitha Nagrath; Lecia V Sequist; Shyamala Maheswaran; Daphne W Bell; Daniel Irimia; Lindsey Ulkus; Matthew R Smith; Eunice L Kwak; Subba Digumarthy; Alona Muzikansky; Paula Ryan; Ulysses J Balis; Ronald G Tompkins; Daniel A Haber; Mehmet Toner Journal: Nature Date: 2007-12-20 Impact factor: 49.962
Authors: Oscar B Goodman; Louis M Fink; James T Symanowski; Bryan Wong; Beth Grobaski; David Pomerantz; Yupo Ma; David C Ward; Nicholas J Vogelzang Journal: Cancer Epidemiol Biomarkers Prev Date: 2009-06 Impact factor: 4.254
Authors: Johann S de Bono; Howard I Scher; R Bruce Montgomery; Christopher Parker; M Craig Miller; Henk Tissing; Gerald V Doyle; Leon W W M Terstappen; Kenneth J Pienta; Derek Raghavan Journal: Clin Cancer Res Date: 2008-10-01 Impact factor: 12.531
Authors: Utsav Sharma; Kelsie Medina-Saenz; Philip C Miller; Benjamin Troness; Angela Spartz; Ana Sandoval-Leon; Deanna N Parke; Tiffany N Seagroves; Marc E Lippman; Dorraya El-Ashry Journal: Breast Cancer Res Treat Date: 2021-07-03 Impact factor: 4.872
Authors: Nerymar Ortiz-Otero; Jocelyn R Marshall; Antonio Glenn; Jubin Matloubieh; Jean Joseph; Deepak M Sahasrabudhe; Edward M Messing; Michael R King Journal: BMC Cancer Date: 2021-08-06 Impact factor: 4.430
Authors: Heather H Cheng; Patrick S Mitchell; Evan M Kroh; Alexander E Dowell; Lisly Chéry; Javed Siddiqui; Peter S Nelson; Robert L Vessella; Beatrice S Knudsen; Arul M Chinnaiyan; Kenneth J Pienta; Colm Morrissey; Muneesh Tewari Journal: PLoS One Date: 2013-07-30 Impact factor: 3.240
Authors: Christopher L Yankaskas; Kaustav Bera; Konstantin Stoletov; Selma A Serra; Julia Carrillo-Garcia; Soontorn Tuntithavornwat; Panagiotis Mistriotis; John D Lewis; Miguel A Valverde; Konstantinos Konstantopoulos Journal: Sci Adv Date: 2021-07-09 Impact factor: 14.136