RRC ID 52667
Author Yamakawa D, Jia W, Kidoya H, Hosojima S, Torigata M, Zhang L, Takakura N.
Title Visualization of Proliferative Vascular Endothelial Cells in Tumors in Vivo by Imaging Their Partner of Sld5-1 Promoter Activity.
Journal Am. J. Pathol.
Abstract Vascular endothelial cells (ECs) isolated from tumors characteristically express certain genes. It has recently been suggested that tumor vessel normalization facilitates effective drug delivery into tumors; however, how tumor vessel normalization can be recognized on the basis of the molecules expressed by tumor ECs is not clearly defined. The degree of cell proliferation is an important indicator to characterize the condition of the ECs. Herein, we generated transgenic mice expressing enhanced green fluorescent protein (EGFP) under the transcriptional control of the DNA replication factor partner of Sld5-1 (PSF1; official name GINS1) promoter to assess whether active ECs can be distinguished from dormant ECs. Predictably, ECs in the adult skin exhibited no EGFP signals. However, after s.c. injection of tumor cells, some ECs shifted to EGFP positivity, enabling distinction of EGFP-positive from EGFP-negative cells. We found that only a fraction of the EGFP-negative ECs strongly expressed the glycosylphosphatidylinositol-anchor protein CD109 associated with the phosphatidylinositol 3-kinase pathway. Taken together, these data indicate that areas of vascular normalization in tumors can be detected by CD109 expression, and this provides a window of opportunity for timing chemotherapy.
Volume 188(5)
Pages 1300-1314
Published 2018-5
DOI 10.1016/j.ajpath.2018.01.015
PII S0002-9440(17)30785-X
PMID 29650228
MeSH Animals Carrier Proteins / genetics Carrier Proteins / metabolism* Cell Line, Tumor Endothelial Cells / metabolism* Endothelial Cells / pathology Mice Microscopy, Fluorescence Neoplasm Transplantation Promoter Regions, Genetic*
IF 3.762
Human and Animal Cells LLC(RCB0558)