Apoptosis of circulating tumor cells in prostate cancer patients.
BACKGROUND
The prescence of circulating tumor cells (CTCs) in the peripheral blood of cancer patients and their frequency has been correlated with disease status.


METHODS
In this study, CTCs were characterized by flow cytometry and fluorescence microscopy after immunomagnetic enrichment from 7.5-ml blood samples collected from patients with prostate cancer in evacuated blood-draw tubes that contained an anticoagulant and a preservative. Events were classified as tumor cell candidates if they expressed cytokeratin, lacked CD45, and stained with the nucleic acid dye 4,6-diamidino-2-phenylindole.


RESULTS
In the blood of prostate cancer patients, only few of these events were intact cells. Other CTC events appeared as damaged cells or cell fragments by microscopy. By flow cytometry, these events stained variably with 4,6-diamidino-2-phenylindole and frequently expressed the apoptosis-induced, caspase-cleaved cytokeratin 18. Similar patterns of cell disintegration were observed when cells of the prostate line LNCaP were exposed to paclitaxel before spiking the cells into normal blood samples.


CONCLUSIONS
The different observed stages of tumor cell degradation or apoptosis varied greatly between patients and were not found in blood of normal donors. Enumeration of CTCs and identification of CTCs undergoing apoptosis may provide relevant information to evaluate the response to therapy in cancer patients.
Immunicon Corporation, Huntingdon Valley, PA 19006, USA.
Christopher J
CJ
Larson
Jose G
JG
Moreno
Kenneth J
KJ
Pienta
Steve
S
Gross
Madeline
M
Repollet
S Mark
SM
O'hara
Thomas
T
Russell
Leon W M M
LW
Terstappen
D000230:Adenocarcinoma / Q000097:blood / Q000737:chemistry / Q000556:secondary*; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis; D002452:Cell Count; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000737:chemistry / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000097:blood / Q000737:chemistry / Q000473:pathology*
D014408:Biomarkers, Tumor