Antibodies to heat-shock protein 27 are associated with improved survival in patients with breast cancer

Abstract

Antibodies to heat-shock protein 27 Summary The overexpression of the heat-shock proteins hsp9O, hsp70 and hsp27 in human mammary carcinomas has previously been shown to correlate with reduced overall survival. Moreover, antibodies to hsp9O were detectable in the serum of a large proportion of breast cancer patients but they were not found in normal controls. High antibody levels also correlated with reduced survival. Here, we show that antibodies to hsp27 were also detectable in the sera from breast cancer patients but not from normal controls, whereas antibodies to hsp70 were detectable in approximately one-third of both groups. The presence of antibodies to hsp27 was correlated with an improved rather than a reduced survival, particularly beyond the first 5 years. Hence, the overexpression of hsps in breast cancer cells does not provoke a generalized immune response to all the hsps. Moreover, the presence of antibodies to different hsps has distinct associations with survival. These effects are discussed in terms of the mechanisms that provoke an immune response to the hsps and the protective/non-protective effects of such a response.

Exogenous heat shock protein 27 uniquely blocks differentiation of monocytes to dendritic cells

“…However, HSP-27-mediated inhibition of MO?iDC differentiation and subsequent DC activation of T cells may also be pathologically dampening immune responses to tumor antigens. This HSP-27 inhibitory effect may explain some of the association of circulating HSP-27 levels with tumor progression [1,3,5].…”

“…IL-10 also depresses macrophage (MU) production of proinflammatory cytokines [16]. An exogenous in vivo anti-inflammatory/immunosuppressive effect of exogenous HSP-27 is also suggested by data showing that circulating antibodies to HSP-27 and/or lower circulating HSP-27 levels (released by necrosis or cytokine induction of MO) were associated with improved cancer patient survival or decreased inflammation in aging and sepsis [1,4,5,17,18]. These HSP-27 immunomodulatory effects might be independent and/or dependent on IL-10 induction.…”

“…Circulating large and small heat shock proteins (HSP) are implicated as modulating adaptive and innate immunity in a variety of disease and inflammatory pathologies beyond their defined chaperone effects [1][2][3][4][5][6][7][8]. Large HSP are thought to act as endogenous danger signals augmenting inflammatory cytokines by triggering monocyte (MO) Toll-like receptors (TLR) and scavenger receptors independently of LPS contaminants [6,7,[9][10][11].…”

Prognostic significance of heat shock protein-27 expression in hepatocellular carcinoma and its relation to histologic grading and survival

“…[17][18][19][20] Recent studies report HSP-27 to be a prognostic factor in certain tumors such as breast carcinoma, astrocytic brain tumors, and malignant fibrous histiocytoma. [21][22][23][24][25][26] Expression of HSP-27 also has been detected in chemically induced rat HCC, 27 and in seven of eight human HCC tissues. 14 However, to our knowledge, its detailed clinicopathologic significance still is not clear.…”

Hsp27 Promotes Igf-1 Survival Signaling in Prostate Cancer via P90rsk-Dependent Phosphorylation and Inactivation of Bad

“…Hsp27 is a stress-induced molecular chaperone that is highly and uniformly expressed in CRPC (13,14) and other cancers (15) (16) (17) and is often associated with metastasis and poor prognosis (18,19). Hsp27 expression is induced by hormone-or chemo-therapy and inhibits treatment-induced apoptosis through multiple mechanisms (8,18,(20)(21)(22).…”