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The role of the intravascular microenvironment in spontaneous metastasis development
Author(s) -
Zhang Qingbei,
Yang Meng,
Shen Jikun,
Gerhold Lynnette M.,
Hoffman Robert M,
Xing H.Rosie
Publication year - 2010
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24979
Subject(s) - extravasation , metastasis , medicine , pathology , cancer , cancer cell , parenchyma , tumor microenvironment , cancer research
Metastasis is primarily responsible for the morbidity and mortality of cancer. Improved therapeutic outcomes and prognosis depend on improved understanding of mechanisms regulating the establishment of early metastasis. In this study, use of green fluorescent protein (GFP)‐expressing PC‐3 orthotopic model of human prostate cancer and two complementary fluorescence in vivo imaging systems (Olympus OV100 and VisEn FMT) allowed for the first time real‐time characterization of cancer cell–endothelium interactions during spontaneous metastatic colonization of the liver and lung in live mice. We observed that prior to the detection of extra‐vascular metastases, GFP‐expressing PC‐3 cancer cells resided initially inside the blood vessels of the liver and the lung, where they proliferated and expressed Ki‐67 and exhibited matrix metalloprotenases (MMP) activity. Thus, the intravascular cancer cells produced their own microenvironment, where they could continue to proliferate. Extravasation occurred earlier in the lung than in the liver. Our results demonstrate that the intravascular microenvironment is a critical staging area for the development of metastasis that later can invade the parenchyma. Intravascular tumor cells may represent a therapeutic target to inhibit the development of extravascular metastases. Therefore, this imageable model of intravascular metastasis may be used for evaluation of novel anti‐metastatic agents.