title: Adrenomedullin in the growth modulation and differentiation of acute myeloid leukemia cells.
abstract: Adrenomedullin (ADM) is a regulatory peptide endowed with multiple biological effects, including the regulation of blood pressure, cell growth and innate host defence. In the present study, we demonstrated that ADM signaling could be involved in the impaired cellular differentiation of myeloid leukemia cells to mature granulocytes or monocytes by modulating RAMPs/CRLR expression, PI3K/Akt cascade and the ERK/MAPK signaling pathway. When exogenously administered to in vitro cultures of HL60 promyelocytic leukemia cells, ADM was shown to exert a strong proliferative effect with minimal upregulation in the expression level of monocyte antigen CD14. Notably, the experimental inhibition of ADM signaling with inhibitor ADM22-52 promoted a differentiative stimulation towards monocytic and granulocytic lineages. Moreover, based on the expression of CD31 relative to CD38, we hypothesized that an excess of ADM in bone marrow (BM) niche could increase the transendothelial migration of leukemia cells while any inhibitory event of ADM activity could raise cell retention in hyaluronate matrix by upregulating CD38. Taken into consideration the above evidence, we concluded that ADM and ADM22-52 could differently affect the growth of leukemia cells by autocrine/paracrine mechanisms and may have clinical relevance as biological targets for the intervention of tumor progression.
authors: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
authors: Rosa
authors: R
authors: Di Liddo
authors: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
authors: Deborah
authors: D
authors: Bridi
authors: Department of Haematology, General Hospital, Treviso, Italy.
authors: Michele
authors: M
authors: Gottardi
authors: Treviso Cord Blood Bank and Hematopoietic Cell Culture Laboratory, Transfusional Center, General Hospital, Treviso, Italy.
authors: Sergio
authors: S
authors: De Angeli
authors: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
authors: Claudio
authors: C
authors: Grandi
authors: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
authors: Alessia
authors: A
authors: Tasso
authors: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
authors: Thomas
authors: T
authors: Bertalot
authors: Institute of Haematology 'L. and A. Seràgnoli', Department of Experimental, Diagnostic and Specialty Medicine, 'S. Orsola-Malpighi' University Hospital, University of Bologna, Bologna, Italy.
authors: Giovanni
authors: G
authors: Martinelli
authors: Department of Haematology, General Hospital, Treviso, Italy.
authors: Filippo
authors: F
authors: Gherlinzoni
authors: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
authors: Maria Teresa
authors: MT
authors: Conconi
mesh_terms: D053607:Adrenomedullin / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000473:pathology*; D020935:MAP Kinase Signaling System
chemical_list: C507862:ADM protein, human; D053607:Adrenomedullin