Real-time in vivo dual-color imaging of intracapillary cancer cell and nucleus deformation and migration.
The mechanism of cancer cell deformation and migration in narrow vessels is incompletely understood. In order to visualize the cytoplasmic and nuclear dynamics of cells migrating in capillaries, red fluorescent protein was expressed in the cytoplasm, and green fluorescent protein, linked to histone H2B, was expressed in the nucleus of cancer cells. Immediately after the cells were injected in the heart of nude mice, a skin flap on the abdomen was made. With a color CCD camera, we could observe highly elongated cancer cells and nuclei in capillaries in the skin flap in living mice. The migration velocities of the cancer cells in the capillaries were measured by capturing images of the dual-color fluorescent cells over time. The cells and nuclei in the capillaries elongated to fit the width of these vessels. The average length of the major axis of the cancer cells in the capillaries increased to approximately four times their normal length. The nuclei increased their length 1.6 times in the capillaries. Cancer cells in capillaries over 8 microm in diameter could migrate up to 48.3 microm/hour. The data suggests that the minimum diameter of capillaries where cancer cells are able to migrate is approximately 8 microm. The use of the dual-color cancer cells differentially labeled in the cytoplasm and nucleus and associated fluorescent imaging provide a powerful tool to understand the mechanism of cancer cell migration and deformation in small vessels.
Yamauchi
Kensuke
K
AntiCancer, Inc., San Diego, California 92111, USA.
Yang
Meng
M
Jiang
Ping
P
Yamamoto
Norio
N
Xu
Mingxu
M
Amoh
Yasuyuki
Y
Tsuji
Kazuhiko
K
Bouvet
Michael
M
Tsuchiya
Hiroyuki
H
Tomita
Katsuro
K
Moossa
A R
AR
Hoffman
Robert M
RM
D000818:Animals; D002196:Capillaries / Q000473:pathology; D002465:Cell Movement / Q000502:physiology*; D002467:Cell Nucleus / Q000473:pathology*; D005354:Fibrosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005453:Fluorescence; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006657:Histones / Q000737:chemistry; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D014161:Transduction, Genetic; D014183:Transplantation, Heterologous; D000097573:Red Fluorescent Protein
D049452:Green Fluorescent Proteins; D006657:Histones; D008164:Luminescent Proteins; D000097573:Red Fluorescent Protein