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PMID: 7905790 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Transfection of the mouse ICAM-1 gene into murine neuroblastoma enhances susceptibility to lysis, reduces in vivo tumorigenicity and decreases ICAM-2-dependent killing.

Cancer immunology, immunotherapy : CII ·Vol. 38 ·No. 2 ·1994-02-00 ·Pages 135-41

Katsanis E, Bausero MA, Xu H, Orchard PJ, Xu Z, McIvor RS, Brian AA, Blazar BR

Abstract

We determined the expression of intercellular adhesion molecules (ICAM) on neuro-2a cells in order to evaluate whether they were involved in cytolysis of murine neuroblastoma. Fluorescence-activated cell sorting analysis revealed that the control neomycin-resistance-gene-transduced line (neuro-2a/LN) had poor expression of ICAM-1 (mean channel fluorescence, MCF = 3.7). An ICAM-1-positive transfectant of neuro-2a (neuro-2a/ICAM-1+) (MCF = 64.3) was generated to evaluate directly the role of this adhesion molecule in cytolysis. Neuro-2a/ICAM-1+ was more sensitive to LAK killing (69.7% at an effector-to-target ratio of 100:1) compared to neuro-2a/LN (48.6%) (P < 0.001). Blocking of neuro-2a/LN and neuro-2a/ICAM-1+ lysis with anti-ICAM-1 monoclonal antibodies (mAbs) did not account for all the LFA-1-dependent killing. These data indicate that even in neuro-2a/ICAM-1+ cells, other LFA-1 ligands participated in the effector-target interaction. Therefore, we examined these cell lines for ICAM-2 expression. Both neuro-2a/LN and neuro-2a/ICAM-1+ lines expressed ICAM-2 (MCF = 16.4 and 16.5). ICAM-2 accounted for the majority of the LFA-1-dependent killing in the ICAM-1-negative target, neuro-2a/LN, while ICAM-1 played a primary role in the cytolysis of the ICAM-1+ transfectant. Inhibition of lysis in the presence of anti-ICAM-1 and ICAM-2 mAbs was comparable to that seen with the addition of anti-LFA-1 mAb, indicating that other LFA-1 ligands were not involved in this system. ICAM-1 expression was associated with decreased in vivo tumorigenicity, mice inoculated with neuro-2a/ICAM-1+ cells had a significantly longer survival compared to those receiving neuro-2a/LN cells (median survival time 35.5 versus 24.5 days) (P < 0.001). It is important to note that ICAM-1 transfection of murine neuroblastoma did not alter its metastatic potential. We conclude that transfection of mouse neuroblastoma with ICAM-1 increases its sensitivity to in vitro lysis and reduces its in vivo tumorigenicity. In ICAM-1-negative murine neuroblastoma cells, ICAM-2 plays a primary role in cell-mediated lysis.

MeSH Terms
Animals Antigens, CD Cell Adhesion Molecules/genetics,immunology Cytotoxicity, Immunologic Immunity, Cellular In Vitro Techniques Intercellular Adhesion Molecule-1 Interleukin-2/pharmacology Killer Cells, Lymphokine-Activated/immunology Mice Mice, Inbred A Neoplasm Metastasis Neuroblastoma/immunology,pathology Transfection Tumor Cells, Cultured
Chemicals
Antigens, CD Cell Adhesion Molecules ICAM2 protein, human Interleukin-2 Intercellular Adhesion Molecule-1
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Katsanis E
Department of Pediatrics, University of Minnesota, Minneapolis 55455.
Bausero M A
Xu H
Orchard P J
Xu Z
McIvor R S
Brian A A
Blazar B R
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Article Info
Journal
Cancer immunology, immunotherapy : CII
Abbr.
Cancer Immunol Immunother
ISSN
0340-7004
DOI
10.1007/BF01526209
Published
1994-02-00
Pages
135-41
Language
English
Region
Germany
NLM ID
8605732
Subset
IM
Grants
NIAID NIH HHS · N01-AI-85002 · United States
NCI NIH HHS · P01-CA-21737 · United States
External Links
PubMed source DOI: 10.1007/BF01526209 View journal details
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