Role of prolactin receptor and CD25 in protection of circulating T lymphocytes from apoptosis in patients with breast cancer

Abstract

Prolactin (PRL) has been reported to inhibit apoptosis in various cell types and to serve as a cofactor in the upregulation of CD25 on T cells during activation. We investigated a possible relation between prolactin receptor (PRL-R) or IL-2 receptor alpha (IL-2Ra, CD25) expression on circulating T lymphocytes and their apoptosis in patients with breast cancer. Peripheral blood mononuclear cells obtained from 25 patients, 25 normal controls (NC) and three cord blood samples were evaluated for Annexin V binding and expression of CD95, CD25, and PRL-R on CD3 + T cells by multicolour flow cytometry. Plasma levels of PRL, sCD95L, and sIL-2R were determined in patients and controls and related to T-cell apoptosis. The ability of PRL to protect T cells from apoptosis induced by various agents was also studied. Expression of PRL-R on the surface of T cells was comparable in patients with breast cancer and NC, but PRL plasma levels in patients were significantly lower (Po0.05). In patients, 18711% (mean7s.d.) of CD3 + cells bound Annexin V, compared to 976% in NC (Po0.0004). Percentages of CD3 + Fas + and CD3 + CD25 + cells were higher in the peripheral circulation of patients than NC (Po0.0001 and o0.04, respectively). Levels of sFasL were lowest in plasma of the patients with the highest proportions of CD3 + Fas + T cells. Most T cells undergoing apoptosis were CD3 + CD25 À in patients, and the proportion of CD3 + CD25 À Annexin V + cells was significantly increased in patients compared to NC (Po0.006). Ex vivo PRL protected T cells from starvation-induced or anti-CD3Ab-induced but not from Fas/FasL-dependent apoptosis. These results indicate that expression of CD25 but not of PRL-R on the surface of activated T lymphocytes appears to be involved in modulating Fas/Fas -ligand interactions, which are, in part, responsible for apoptosis of T lymphocytes and excessive turnover of immune cells in the circulation of patients with breast cancer.

Prolactin: A versatile regulator of inflammation and autoimmune pathology

“…In line with these data, we did not detect PRL at either mRNA or protein levels in mouse primary CD4 + T cells [35]. In human T cells, PRL has been proposed to support proliferation [36], survival [37], and to act as an autocrine factor. Indeed, an extrapituitary PRL transcript has been found in human T cells [38], and its levels are increased following stimulation with cyclic AMP [39], as well as in PBMCs and Jurkat T cell line after treatment with prostaglandin E 2 [40,41].…”

Prolactin: Friend or Foe in Central Nervous System Autoimmune Inflammation?

“…PRL also supports the maturation of dendritic cells derived from monocytic precursors, promoting the expression of MHC class II and CD80/86 co-stimulatory molecules [33,34]. PRL has been proposed as an autocrine factor sustaining survival and proliferation of human T cells [35,36]. On the contrary, no Prl transcript or protein have been detected in purified CD4 + T cell cultures of mouse origin [37].…”

Carboxypeptidase-D is elevated in prostate cancer and its anti-apoptotic activity is abolished by combined androgen and prolactin receptor targeting

“…There is evidence suggesting that prolactin (PRL) and the PRL receptor (PRLR) signaling pathway may be one such alternate . PRL is a trophic polypeptide hormone and, acting through the PRLR, is involved in anti‐apoptosis and/or proliferation in many target tissues and cell types , including the prostate . While PRL is produced mainly in the pituitary, it is also produced locally in prostate epithelium, where it acts as an autocrine/paracrine growth factor, due to the expression of the PRLR in the prostate .…”