Role of Prolactin Receptor and CD25 in Protection of Circulating T Lymphocytes from Apoptosis in Patients with Breast Cancer

Overview

Journal Br J Cancer

Specialty Oncology

Date 2003 Apr 17

PMID 12698200

Citations 6

Authors

T Bauernhofer

I Kuss

U Friebe-Hoffmann

A S Baum

G Dworacki

B K Vonderhaar

T L Whiteside

Affiliations

Soon will be listed here.

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-2Ralpha, 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 (P<0.05). In patients, 18+/-11% (mean+/-s.d.) of CD3(+) cells bound Annexin V, compared to 9+/-6% in NC (P<0.0004). Percentages of CD3(+)Fas(+) and CD3(+)CD25(+) cells were higher in the peripheral circulation of patients than NC (P<0.0001 and <0.04, 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(-) in patients, and the proportion of CD3(+)CD25(-) Annexin V(+) cells was significantly increased in patients compared to NC (P<0.006). 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.

Citing Articles

The effects of postoperative targeted immunotherapy on peripheral blood cytokines and immune cell profile in lung cancer patients.

Zhang C, Mo H, Li M, Wang S, Dou X, Zhang X Front Oncol. 2024; 14:1342624.

PMID: 38903721 PMC: 11188683. DOI: 10.3389/fonc.2024.1342624.

The Peripheral Immune Landscape of Breast Cancer: Clinical Findings and In Vitro Models for Biomarker Discovery.

Batalha S, Ferreira S, Brito C Cancers (Basel). 2021; 13(6).

PMID: 33804027 PMC: 8001103. DOI: 10.3390/cancers13061305.

Prolactin Rescues Immature B Cells from Apoptosis-Induced BCR-Aggregation through STAT3, Bcl2a1a, Bcl2l2, and Birc5 in Lupus-Prone MRL/lpr Mice.

Flores-Fernandez R, Aponte-Lopez A, Suarez-Arriaga M, Gorocica-Rosete P, Pizana-Venegas A, Chavez-Sanchez L Cells. 2021; 10(2).

PMID: 33557010 PMC: 7913714. DOI: 10.3390/cells10020316.

Extrapituitary prolactin promotes generation of Eomes-positive helper T cells mediating neuroinflammation.

Zhang C, Raveney B, Hohjoh H, Tomi C, Oki S, Yamamura T Proc Natl Acad Sci U S A. 2019; 116(42):21131-21139.

PMID: 31570595 PMC: 6800326. DOI: 10.1073/pnas.1906438116.

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

Costanza M, Pedotti R Int J Mol Sci. 2016; 17(12).

PMID: 27918427 PMC: 5187826. DOI: 10.3390/ijms17122026.

References

Clevenger C, Freier D, Kline J . Prolactin receptor signal transduction in cells of the immune system. J Endocrinol. 1998; 157(2):187-97. DOI: 10.1677/joe.0.1570187. View

Matera L, Cesano A, Bellone G, Oberholtzer E . Modulatory effect of prolactin on the resting and mitogen-induced activity of T, B, and NK lymphocytes. Brain Behav Immun. 1992; 6(4):409-17. DOI: 10.1016/0889-1591(92)90039-q. View

Clevenger C, Russell D, Appasamy P, Prystowsky M . Regulation of interleukin 2-driven T-lymphocyte proliferation by prolactin. Proc Natl Acad Sci U S A. 1990; 87(16):6460-4. PMC: 54554. DOI: 10.1073/pnas.87.16.6460. View

Darzynkiewicz Z, Bruno S, Del Bino G, Gorczyca W, Hotz M, Lassota P . Features of apoptotic cells measured by flow cytometry. Cytometry. 1992; 13(8):795-808. DOI: 10.1002/cyto.990130802. View

Badley A, Dockrell D, Algeciras A, Ziesmer S, Landay A, Lederman M . In vivo analysis of Fas/FasL interactions in HIV-infected patients. J Clin Invest. 1998; 102(1):79-87. PMC: 509068. DOI: 10.1172/JCI2691. View

ONeal K, Schwarz L . Prolactin receptor gene expression in lymphoid cells. Mol Cell Endocrinol. 1991; 82(2-3):127-35. DOI: 10.1016/0303-7207(91)90023-l. View

Banerjee R, Ginsburg E, Vonderhaar B . Characterization of a monoclonal antibody against human prolactin receptors. Int J Cancer. 1993; 55(5):712-21. DOI: 10.1002/ijc.2910550503. View

Ju S, Panka D, Cui H, Ettinger R, El-Khatib M, Sherr D . Fas(CD95)/FasL interactions required for programmed cell death after T-cell activation. Nature. 1995; 373(6513):444-8. DOI: 10.1038/373444a0. View

Hoffmann T, Dworacki G, Tsukihiro T, Meidenbauer N, Gooding W, Johnson J . Spontaneous apoptosis of circulating T lymphocytes in patients with head and neck cancer and its clinical importance. Clin Cancer Res. 2002; 8(8):2553-62. View

10.

Kuss I, Saito T, Johnson J, Whiteside T . Clinical significance of decreased zeta chain expression in peripheral blood lymphocytes of patients with head and neck cancer. Clin Cancer Res. 1999; 5(2):329-34. View

11.

Lavoie H, Witorsch R . Investigation of intracellular signals mediating the anti-apoptotic action of prolactin in Nb2 lymphoma cells. Proc Soc Exp Biol Med. 1995; 209(3):257-69. DOI: 10.3181/00379727-209-43901. View

12.

Matera L, Cutufia M, Geuna M, Contarini M, Buttiglieri S, Galin S . Prolactin is an autocrine growth factor for the Jurkat human T-leukemic cell line. J Neuroimmunol. 1997; 79(1):12-21. DOI: 10.1016/s0165-5728(97)00096-9. View

13.

Bazan J . A novel family of growth factor receptors: a common binding domain in the growth hormone, prolactin, erythropoietin and IL-6 receptors, and the p75 IL-2 receptor beta-chain. Biochem Biophys Res Commun. 1989; 164(2):788-95. DOI: 10.1016/0006-291x(89)91528-3. View

14.

Dardenne M, de Moraes M, Kelly P, Gagnerault M . Prolactin receptor expression in human hematopoietic tissues analyzed by flow cytofluorometry. Endocrinology. 1994; 134(5):2108-14. DOI: 10.1210/endo.134.5.8156910. View

15.

Muschen M, Moers C, Warskulat U, Even J, Niederacher D, Beckmann M . CD95 ligand expression as a mechanism of immune escape in breast cancer. Immunology. 2000; 99(1):69-77. PMC: 2327134. DOI: 10.1046/j.1365-2567.2000.00921.x. View

16.

Peter M, Kischkel F, Scheuerpflug C, Medema J, Debatin K, Krammer P . Resistance of cultured peripheral T cells towards activation-induced cell death involves a lack of recruitment of FLICE (MACH/caspase 8) to the CD95 death-inducing signaling complex. Eur J Immunol. 1997; 27(5):1207-12. DOI: 10.1002/eji.1830270523. View

17.

Gala R, Shevach E . Influence of prolactin and growth hormone on the activation of dwarf mouse lymphocytes in vivo. Proc Soc Exp Biol Med. 1993; 204(2):224-30. DOI: 10.3181/00379727-204-43657. View

18.

Weimann E, Baixeras E, Zamzami N, Kelly P . Prolactin blocks glucocorticoid induced cell death by inhibiting the disruption of the mitochondrial membrane. Leuk Res. 1999; 23(8):751-62. DOI: 10.1016/s0145-2126(99)00050-8. View

19.

Chen X, Woiciechowsky A, Raffegerst S, Schendel D, Kolb H, Roskrow M . Impaired expression of the CD3-zeta chain in peripheral blood T cells of patients with chronic myeloid leukaemia results in an increased susceptibility to apoptosis. Br J Haematol. 2000; 111(3):817-25. View

20.

Woo E, Chu C, Goletz T, Schlienger K, Yeh H, Coukos G . Regulatory CD4(+)CD25(+) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer. Cancer Res. 2001; 61(12):4766-72. View