Characterization of circulating tumor cell aggregates identified in patients with epithelial tumors.
Circulating tumor cells (CTCs) have been implicated as a population of cells that may seed metastasis and venous thromboembolism (VTE), two major causes of mortality in cancer patients. Thus far, existing CTC detection technologies have been unable to reproducibly detect CTC aggregates in order to address what contribution CTC aggregates may make to metastasis or VTE. We report here an enrichment-free immunofluorescence detection method that can reproducibly detect and enumerate homotypic CTC aggregates in patient samples. We identified CTC aggregates in 43% of 86 patient samples. The fraction of CTC aggregation was investigated in blood draws from 24 breast, 14 non-small cell lung, 18 pancreatic, 15 prostate stage IV cancer patients and 15 normal blood donors. Both single CTCs and CTC aggregates were measured to determine whether differences exist in the physical characteristics of these two populations. Cells contained in CTC aggregates had less area and length, on average, than single CTCs. Nuclear to cytoplasmic ratios between single CTCs and CTC aggregates were similar. This detection method may assist future studies in determining which population of cells is more physically likely to contribute to metastasis and VTE.
Department of Cell Biology, The Scripps Research Institute, 10666 North Torrey Pines Road, GAC-1200, La Jolla, CA 92037, USA. echojhu@gmail.com
Edward H
EH
Cho
Marco
M
Wendel
Madelyn
M
Luttgen
Craig
C
Yoshioka
Dena
D
Marrinucci
Daniel
D
Lazar
Ethan
E
Schram
Jorge
J
Nieva
Lyudmila
L
Bazhenova
Alison
A
Morgan
Andrew H
AH
Ko
W Michael
WM
Korn
Anand
A
Kolatkar
Kelly
K
Bethel
Peter
P
Kuhn
D000328:Adult; D015331:Cohort Studies; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007211:Indoles / Q000737:chemistry; D007633:Keratins / Q000737:chemistry; D009362:Neoplasm Metastasis / Q000175:diagnosis / Q000473:pathology; D009375:Neoplasms, Glandular and Epithelial / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*
D007211:Indoles; C007293:DAPI; D007633:Keratins