Expression of prolactin and prolactin receptors by non-Hodgkin's lymphoma cells.
Prolactin (PRL) interacts with lymphocyte-signaling molecules and cytokines. Previous work has shown independent and synergistic effects of PRL on the generation of IL-2-driven anti-tumor lymphokine activated killer (LAK) activity by peripheral blood mononuclear cells (PBMC). The potential importance of PRL as a biological immunomodifier, however, is challenged by its ability to influence normal lymphocyte mitogenesis and hence lymphoid tumor growth. Since non-Hodgkin's lymphoma (NHL) cell lines were efficiently killed by LAK generated with native (n) or recombinant (r) human PRL combined with low, per se ineffective doses of IL-2, we have addressed here the question of whether PRL acts as a growth factor for LAK targets. NHL cells were analyzed for: 1. expression of the PRL receptor (PRL-R); 2. responsiveness to nPRL or rPRL; 3. constitutive expression and release of PRL; 4. existence of a PRL autocrine loop. PRL-R, defined by multiple antibodies, was detected in 3 of 12 NHL cell lines. However, nPRL or rPRL, in a wide range of concentrations (0.75-50 ng/ml), were not mitogenic for growth-arrested, PRL-R positive NHL cell lines. PRL mRNA was detected by RT-PCR in 10 of the 12 cell lines examined with a higher frequency among AIDS-related NHL cell lines. PRL protein in the immunoprecipitate of (35)S-methionine-labeled cell lysates and supernatants paralleled mRNA expression, and Western blotting analysis showed the presence of the pituitary/lymphocyte non-glycosylated (23.5 kDa) and glycosylated (25 kDa) isoforms. Experiments with blocking antibodies showed the independence from endogenous PRL for NHL cell growth.
Matera
L
L
Department of Internal Medicine, University of Turin, Turin, Italy. matera@molinette.unito.it
Geuna
M
M
Pastore
C
C
Buttiglieri
S
S
Gaidano
G
G
Savarino
A
A
Marengo
S
S
Vonderhaar
B K
BK
D019138:Antibodies, Blocking / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001345:Autoradiography; D015153:Blotting, Western; D005434:Flow Cytometry; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism* / Q000473:pathology; D008938:Mitosis / Q000187:drug effects; D011388:Prolactin / Q000096:biosynthesis* / Q000378:metabolism / Q000494:pharmacology; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011981:Receptors, Prolactin / Q000096:biosynthesis* / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016196:S Phase / Q000187:drug effects; D014407:Tumor Cells, Cultured
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D020033:Protein Isoforms; D012333:RNA, Messenger; D011981:Receptors, Prolactin; D011994:Recombinant Proteins; D011388:Prolactin