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Differential expression of Hela‐type caldesmon in tumour neovascularization: a new marker of angiogenic endothelial cells
Author(s) -
Zheng PingPin,
van der Weiden M,
Kros Johan M
Publication year - 2005
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1700
Subject(s) - caldesmon , biology , hela , pathology , neovascularization , microbiology and biotechnology , alternative splicing , cancer research , angiogenesis , exon , cell , medicine , biochemistry , gene , calmodulin , enzyme
Caldesmon (CaD) is a major actomyosin‐binding protein found in various cell types. There are at least two high‐molecular‐weight isoforms ( h ‐CaD) and four low‐molecular‐weight isoforms ( l ‐CaD) produced by alternative splicing. The alternatively spliced variants of the l ‐CaD class are further differentiated by inclusion (Hela l ‐CaD) or exclusion (WI‐38 l ‐CaD) of exon 1. Currently, nothing is known about differential expression of the Hela l ‐CaD in tumour neovascularization. In a previous study, expression of the Hela‐type transcripts was found in glioma blood vessels but not in the normal cerebral vasculature. To investigate whether the differentially expressed transcripts are translated into protein, a specific antibody against the peptide encoded by exon 1 was raised. Initially, exclusive expression of the protein in glioma vasculature was confirmed. To determine further whether these findings are generalizable to neovascularization in a wide variety of other tumour types, a large cohort of cancers derived from various organs, including breast, lung, kidney, colon, stomach, ovary, uterus, prostate, thyroid, liver, giving a total of 180 cases, were examined. Expression of the Hela l ‐CaD was restricted to tumour vasculature and was not found in normal blood vessels. Hela l ‐CaD was preferentially expressed in the early stage of tumour neovascularization and the Hela l ‐CaD + endothelial cells (ECs) were frequently enlarged, multinucleated, and developed elongated cell projections or free fragments of cytoplasm, correlating with the features of motile cells. In the Hela l ‐CaD + ECs, disassembly of focal adhesion and the formation of podosome‐like structures was observed. Therefore, the findings support the notion that quiescent ECs undergo activation of motility, necessary for ubiquitous tumour‐associated neovascularization. The data indicate that Hela l ‐CaD can be considered as a marker for angiogenic ECs during the early stages of tumour neovascularization. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.