Unexpected deeds of familiar proteins: Interplay of Hsp70, PGRP-S/Tag7 and S100A4/Mts1 in host vs. cancer combat.
We consider the novel means of attack and defense in the host versus cancer combat that involve interactions between widespread multifunctional proteins, focusing on the aspects that may seem paradoxical in the framework of established notions. Particularly, we show that a protein broadly known for its protective functions such as Hsp70 can make a tumoricidal "binary weapon" with another nontoxic protein Tag7 (PGRP-S); that the same Hsp70, a ubiquitous intracellular chaperone, when expressed on the MHC-negative tumor cell surface, can itself be the hallmark of immune evasion rather than a primordial MHC substitute; that a device functionally equivalent to the T-cell receptor (Tag7-Centered Recognizer) can be assembled of components in no way related to the classical pathways of T-cell-mediated immunity, and operate where the orthodox immunosurveillance fails; and that one and the same protein Mts1 (S100A4) under different circumstances may work as "reactive armor" of a tumor cell against humoral agents and as a vital part of the T-cell machinery aimed against immunoevasive cells, i.e., perform both prometastatic and antimetastatic functions.
Dukhanina
Elena A
EA
Laboratory of Molecular Immunogenetics of Cancer, Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia.
Yashin
Denis V
DV
Galkin
Alexander V
AV
Sashchenko
Lidia P
LP
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000627:therapeutic use*; D018840:HSP70 Heat-Shock Proteins / Q000627:therapeutic use*; D006801:Humans; D020014:K562 Cells; D051379:Mice; D008811:Mice, Inbred DBA; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; C491878:PGLYRP1 protein, human; D011948:Receptors, Antigen, T-Cell; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human