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Impact of the coxsackie and adenovirus receptor (CAR) on glioma cell growth and invasion: Requirement for the C‐terminal domain
Author(s) -
Huang KuoCheng,
Altinoz Meric,
Wosik Karolina,
Larochelle Nancy,
Koty Zafiro,
Zhu Lixia,
Holland Paul C.,
Nalbantoglu Josephine
Publication year - 2004
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.20623
Subject(s) - glioma , u87 , cell culture , biology , cell , cell growth , cancer research , microbiology and biotechnology , biochemistry , genetics
Expression of the coxsackie and adenovirus receptor (CAR) is downregulated in malignant glioma cell lines and is barely detectable in high‐grade primary astrocytoma (glioblastoma multiforme). We determined the effect of forced CAR expression on the invasion and growth of the human glioma cell line U87‐MG, which does not express any CAR. Although retrovirally mediated expression of full‐length CAR in U87‐MG cells did not affect monolayer growth in vitro , it did reduce glioma cell invasion in a 3‐dimensional spheroid model. Furthermore, in xenograft experiments, intracerebral implantation of glioma cells expressing full‐length CAR resulted in tumors with a significantly reduced volume compared to tumors generated by control vector‐transduced U87‐MG cells. In contrast, U87‐MG cells expressing transmembrane CAR with a deletion of the entire cytoplasmic domain (except for the first 2 intracellular juxtamembrane cysteine amino acids) had rates of invasion and tumor growth that were similar to those of the control cells. This difference in behavior between the 2 forms of CAR was not due to improper cell surface localization of the cytoplasmically deleted CAR as determined by comparable immunostaining of unpermeabilized cells, equivalent adenoviral transduction of the cells and similar extent of fractionation into lipid‐rich domains. Taken together, these results suggest that the decrease or loss of CAR expression in malignant glioma may confer a selective advantage in growth and invasion to these tumors. © 2004 Wiley‐Liss, Inc.