Urokinase Exerts Antimetastatic Effects by Dissociating Clusters of Circulating Tumor Cells

Cited 28 time in webofscience Cited 0 time in scopus
  • Hit : 303
  • Download : 0
Clusters of circulating tumor cells (CTC) exhibit more robust metastatic properties than single CTC. Thus, understanding the distinct behaviors of CTC clusters and how CTC clustering is regulated may offer new insights into how to limit metastasis. In this study, we utilized an in vivo confocal system to observe the clustering behavior of CTC in real time, finding that the number of clusters increased proportionally with the growth of the primary tumor. Our experiments also indicated that the flow rate of the CTC clusters in blood vessels was relatively slower than single CTC due to increased vessel wall adhesion. Depending on disease stage, 5% to 10% of total CTC in circulation were in clusters, with this proportion increasing to >24% within lung metastases examined. Notably, in the 4T1 mouse model of breast cancer metastasis, we found that injecting host animals with urokinase-type plasminogen activator, a clinical thrombolytic agent, was effective at preventing the assembly of CTC clusters and prolonging overall host survival by approximately 20% relative to control animals. Our results suggest a tractable approach to limit metastasis by suppressing the formation or stability of CTC clusters circulating in the blood of cancer patients.
Publisher
AMER ASSOC CANCER RESEARCH
Issue Date
2015-11
Language
English
Article Type
Article
Keywords

INDUCED PLATELET-AGGREGATION; EXPERIMENTAL METASTASIS; FIBRINOGEN INFLUX; CANCER METASTASIS; PERIPHERAL-BLOOD; BREAST-CANCER; SIZE; THROMBOSIS; SYSTEM; STROMA

Citation

CANCER RESEARCH, v.75, no.21, pp.4474 - 4482

ISSN
0008-5472
DOI
10.1158/0008-5472.CAN-15-0684
URI
http://hdl.handle.net/10203/207852
Appears in Collection
NT-Journal Papers(저널논문)
Files in This Item
There are no files associated with this item.
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 28 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0