原创力文档adamts1 alters blood vessel morphology and tsp1 levels in lncap and lncap-19 prostate tumorsadamts1改变血管形态和常会lncap和lncap-19前列腺肿瘤.pdfVIP
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adamts1 alters blood vessel morphology and tsp1 levels in lncap and lncap-19 prostate tumorsadamts1改变血管形态和常会lncap和lncap-19前列腺肿瘤
Gustavsson et al. BMC Cancer 2010, 10:288
/1471-2407/10/288
R E S E A R C H A R T I C L E Open Access
Research article
ADAMTS1 alters blood vessel morphology and
TSP1 levels in LNCaP and LNCaP-19 prostate
tumors
1 1 1 2 1 1
Heléne Gustavsson , Tajana Tešan , Karin Jennbacken , Kouji Kuno , Jan-Erik Damber and Karin Welén*
Abstract
Background: Decreased expression of the angiogenesis inhibitor ADAMTS1 (ADAM metallopeptidase with
thrombospondin type 1 motif, 1) has previously been reported during prostate cancer progression. The aim of this
study was to investigate the function of ADAMTS1 in prostate tumors.
Methods: ADAMTS1 was downregulated by shRNA technology in the human prostate cancer cell line LNCaP
(androgen-dependent), originally expressing ADAMTS1, and was upregulated by transfection in its subline LNCaP-19
(androgen-independent), expressing low levels of ADAMTS1. Cells were implanted subcutaneously in nude mice and
tumor growth, microvessel density (MVD), blood vessel morphology, pericyte coverage and thrombospondin 1 (TSP1)
were studied in the tumor xenografts.
Results: Modified expression of ADAMTS1 resulted in altered blood vessel morphology in the tumors. Low expression
levels of ADAMTS1 were associated with small diameter blood vessels both in LNCaP and LNCaP-19 tumors, while high
levels of ADAMTS1 were associated with larger vessels. In addition, TSP1 levels in the tumor xenografts were inversely
related to ADAMTS1 expression. MVD and pericyte coverage were not affected. Moreover, upregulation of ADAMTS1
inhibited tumor growth of LNCaP-19, as evidenced by delayed tumor establishment. In contrast, downregulation of
ADAMTS1 in LNCaP resulted in reduced tumor growth rate.
Conclusions: T
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