Opposite roles of metastasin (S100A4) in two potentially tumoricidal mechanisms involving human lymphocyte protein Tag7 and Hsp70

We compare the physical and functional interactions between three widespread multifunctional proteins [metastasin (Mts1/S100A4), innate immunity-related Tag7/PGRP-S, and Hsp70] in two experimental models relevant to host-tumor relationships on humoral and cellular levels. (i) Tag7 and Hsp70 in solut...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2009-08, Vol.106 (33), p.13963-13967
Main Authors: Dukhanina, Elena A, Kabanova, Olga D, Lukyanova, Tamara I, Shatalov, Yury V, Yashin, Denis V, Romanova, Elena A, Gnuchev, Nikolai V, Galkin, Alexander V, Georgiev, Georgii P, Sashchenko, Lidia P
Format: Article
Language:English
Subjects:
Animals
Antibodies
Apoptosis
Biological Sciences
Biotinylation
Blood
CD4-Positive T-Lymphocytes - metabolism
Cell Membrane - metabolism
Cells
Comparative analysis
Cytokines - metabolism
Cytotoxicity
Gels
Gene Expression Regulation, Neoplastic
HSP70 Heat-Shock Proteins - metabolism
Humans
Interleukin-2 Receptor alpha Subunit - metabolism
K562 Cells
Leukocytes, Mononuclear - metabolism
Lymphocytes
Metastasis
Mice
Proteins
S100 Calcium-Binding Protein A4
S100 Proteins - biosynthesis
S100 Proteins - physiology
T lymphocytes
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:We compare the physical and functional interactions between three widespread multifunctional proteins [metastasin (Mts1/S100A4), innate immunity-related Tag7/PGRP-S, and Hsp70] in two experimental models relevant to host-tumor relationships on humoral and cellular levels. (i) Tag7 and Hsp70 in solution or in a lymphocyte make a stable binary complex that is highly cytotoxic for some tumor cells. Here, we show that Mts1 prevents Tag7·Hsp70 assembly in solution, and an excess of Mts1 disrupts the existing Tag7·Hsp70 complex; accordingly, Tag7·Hsp70 cytotoxicity (exemplified with L929 cells) is diminished in the presence of excess Mts1. (ii) Tag7 exposed on a specialized subset of lymphokine-activated killer cells makes specific contact with Hsp70 exposed on some HLA-negative tumor cells, thus enabling FasL/Fas-mediated induction of apoptosis. Here, we show that some CD4⁺CD25⁺ cells coexpose Mts1 with Tag7 and FasL, that Mts1 and Tag7 closely contact the same Hsp70 molecule on the target K562 cell (as evidenced by cross-linking), and that killing of such targets is abolished by Mts1-specific antibodies (or selective removal of Mts1-exposing lymphocytes). Thus, this phenotype active against immunoevasive cancerous cells is defined as CD4⁺CD25⁺, FasL⁺, Tag7⁺Mts1⁺ ([almost equal to]0.5% of total lymphocytes in culture). Remarkably, similar effectors with at least the same activity are often found in fresh donor blood samples ([almost equal to]10⁴ effectors/mL). Thus, our models suggest that interactions between the three proteins in different situations may have opposite functional outcomes as regards antitumor defense, immune escape, and metastasis.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0900116106