Kinetics of Metastatic Breast Cancer Cell Trafficking in Bone

Purpose: In vivo studies have focused on the latter stages of the bone metastatic process (osteolysis), whereas little is known about earlier events, e.g., arrival, localization, and initial colonization. Defining these initial steps may potentially identify the critical points susceptible to therap...

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Bibliographic Details
Published in:Clinical cancer research 2006-03, Vol.12 (5), p.1431-1440
Main Authors: PHADKE, Pushkar A, MERCER, Robyn R, GAY, Carol V, MASTRO, Andrea M, WELCH, Danny R, HARMS, John F, YUJIANG JIA, FROST, Andra R, JEWELL, Jennifer L, BUSSARD, Karen M, NELSON, Shakira, MOORE, Cynthia, KAPPES, John C
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Biological and medical sciences
bone
Bone Neoplasms - secondary
breast cancer
Breast Neoplasms - pathology
Cell Line, Tumor - transplantation
Female
Femur - pathology
Flow Cytometry
Green Fluorescent Proteins - genetics
Gynecology. Andrology. Obstetrics
Humans
Immunohistochemistry
Kinetics
Mammary gland diseases
Medical sciences
metastasis
Mice
Mice, Nude
Microscopy, Fluorescence
osteoblast paralysis
Osteoblasts - pathology
Pharmacology. Drug treatments
Reverse Transcriptase Polymerase Chain Reaction
Tumors
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Summary:Purpose: In vivo studies have focused on the latter stages of the bone metastatic process (osteolysis), whereas little is known about earlier events, e.g., arrival, localization, and initial colonization. Defining these initial steps may potentially identify the critical points susceptible to therapeutic intervention. Experimental Design: MDA-MB-435 human breast cancer cells engineered with green fluorescent protein were injected into the cardiac left ventricle of athymic mice. Femurs were analyzed by fluorescence microscopy, immunohistochemistry, real-time PCR, flow cytometry, and histomorphometry at times ranging from 1 hour to 6 weeks. Results: Single cells were found in distal metaphyses at 1 hour postinjection and remained as single cells up to 72 hours. Diaphyseal arrest occurred rarely and few cells remained there after 24 hours. At 1 week, numerous foci (2-10 cells) were observed, mostly adjacent to osteoblast-like cells. By 2 weeks, fewer but larger foci (≥50 cells) were seen. Most bones had a single large mass at 4 weeks (originating from a colony or coalescing foci) which extended into the diaphysis by 4 to 6 weeks. Little change (
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.CCR-05-1806