Oxytocin is a growth factor for Kaposi's sarcoma cells: evidence of endocrine-immunological cross-talk.
Oxytocin receptors (OTRs) are expressed in numerous tissues, including human normal endothelium. Here we investigated the expression and biological significance of OTRs in Kaposi's sarcoma (KS), an intensely angioproliferative disease of possible vascular origin with a prominent inflammatory component. Immunohistochemistry and in situ hybridization studies showed OTR expression in tumor cells of cutaneous classic and AIDS-related KS lesions. OTR mRNA and protein were also detected on cultured KS-IMM spindle cells by reverse transcription-PCR and immunofluorescence procedures. In these cells, OTR expression was up-regulated by the supernatants of resting CD4+ and CD8+ lymphocytes through a still unidentified factor. Functionality of OTRs was demonstrated because OT treatment of KS-IMM cells led to a significant increase in cell proliferation, coupled to the increase of intracellular calcium, but did not effect cell migration in vitro or angiogenesis in vivo. In addition, we demonstrated that CD4+ and CD8+ cells produce OT themselves, thus constituting an intralesional source of peptide. These results indicate that: (a) functioning OTRs are expressed in KS cells and modulated by the inflammatory counterpart of KS lesions; (b) via OTRs, OT stimulates KS-IMM cell proliferation and could, therefore, be considered a new possible relevant growth factor involved in KS progression; and finally (c) the evidence of OT synthesis by CD4+ and CD8+ lymphocytes strongly suggests the existence of local endocrine-immunological cross-talk in Kaposi's sarcoma.
Cassoni
Paola
P
Department of Biomedical Sciences and Human Oncology, University of Turin, Via Santena 7, 10126 Turin, Italy.
Sapino
Anna
A
Deaglio
Silvia
S
Bussolati
Benedetta
B
Volante
Marco
M
Munaron
Luca
L
Albini
Adriana
A
Torrisi
Antonietta
A
Bussolati
Gianni
G
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis / Q000276:immunology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D010121:Oxytocin / Q000096:biosynthesis / Q000494:pharmacology* / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018045:Receptors, Oxytocin / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012514:Sarcoma, Kaposi / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
D007378:Interleukins; D012333:RNA, Messenger; D018045:Receptors, Oxytocin; D010121:Oxytocin; D002118:Calcium