The present study performed a combination of In vitro and In
vivo tests, examining the role of the AM system on the growth of melanoma cell
lines and xenografts, respectively. Even though targeted medicines and
immunotherapies have made tremendous progress, metastatic melanoma is an
aggressive disease that can provide a serious therapeutic challenge. This
underscores the necessity for the identification of new therapeutic targets.
Adrenomedullin (AM) is a multifunctional peptide that is expressed significantly
in many tumor types. By binding to calcitonin receptor-like receptor/receptor
activity-modifying protein 2 or 3 (CLR/RAMP2; CLR/RAMP3), AM affects
angiogenesis and tumor progression. In vitro and in vivo studies were performed
to determine the functional role of AM in melanoma growth and tumor-associated
angiogenesis and lymphangiogenesis. AM and AM receptors were
immunohistochemically localized in the tumoral compartment of melanoma tissue,
suggesting that the AM system plays a role in melanoma growth. We used A375,
SK-MEL-28, and MeWo cells, for which we demonstrated an expression of AM and
its receptors; hypoxia induces the expression of AM in melanoma cells. The
proliferation of A375 and SK-MEL-28 cells is decreased by anti-AM antibody (αAM) and anti-AMR antibodies
(αAMR), supporting the
fact that AM may function as a potent autocrine/paracrine growth factor for
melanoma cells. Furthermore, migration and invasion of melanoma cells increased
after treatment with AM and decreased after treatment with αAMR, thus indicating that
melanoma cells are regulated by AM. Reduced numbers of vessel structures showed
that systemic administration of αAMR
decreased the neovascularization of in vivo Matrigel plugs containing melanoma
cells. This suggests that AM is one of the factors derived from melanoma cells
that is responsible for endothelial cell-like and pericyte recruitment in the
construction of neovascularization. Tumor regression was achieved in vivo by αAMR treatment, which
inhibited angiogenesis and lymphangiogenesis and reduced proliferation in MeWo
xenografts. Upon histological evaluation, tumors treated with aAMR exhibited indications of disrupted tumor vascularity,
including a notable reduction in lymphatic endothelial cells and a depletion of
vascular endothelial cells. Finally, the representation of AM by melanoma cells
promotes tumor growth and neovascularization by supplying/amplifying signals
for neoangiogenesis and lymphangiogenesis.
Author(s)details:-
Zohra Benyahia
Aix Marseille University, CNRS, INP, Inst Neurophysiopathol, 13005
Marseille, France.
Caroline
Gaudy-Marqueste
Aix Marseille University, APHM, CHU Timone, Service de Dermatologie et de
Cancérologie Cutanée, 13005 Marseille, France.
Caroline
Berenguer-Daizé
Aix Marseille University, CNRS, INP, Inst Neurophysiopathol, 13005
Marseille, France.
Norhimane Chabane
Aix Marseille University, CNRS, INP, Inst Neurophysiopathol, 13005
Marseille, France.
Nadège Dussault
Aix Marseille University, CNRS, INP, Inst Neurophysiopathol, 13005
Marseille, France.
Mylène Cayol
Aix Marseille University, CNRS, INP, Inst Neurophysiopathol, 13005
Marseille, France.
Christine Vellutini
Aix Marseille University, CNRS, INP, Inst Neurophysiopathol, 13005
Marseille, France
Amina Djemli
Aix Marseille University, APHM, CHU Nord, Service D’anatomopathologie,
13015 Marseille, France.
Isabelle Nanni
Aix Marseille University, CNRS, ICR, Institut de Chimie Radicalaire, 13013
Marseille, France.
Nathalie Beaufils
Aix Marseille University, CNRS, ICR, Institut de Chimie Radicalaire, 13013
Marseille, France.
Kamel Mabrouk
Aix Marseille University, APHM, CHU Nord, Service D’Onco-Biologie, 13015
Marseille, France.
Jean-Jacques Grob
Aix Marseille University, APHM, CHU Timone, Service de Dermatologie et de
Cancérologie Cutanée, 13005 Marseille, France.
Please See the book
here :- https://doi.org/10.9734/bpi/mria/v2/8351E
No comments:
Post a Comment