Angiogenic, lymphangiogenic and adipogenic effects of HIV-1 matrix protein p17.
Lymphangiogenesis and concurrent angiogenesis are essential in supporting proliferation and survival of AIDS-related lymphomas, which are often metastatic. In vitro studies suggest a candidate angiogienic and lymphangiogenic factor encoded by HIV: the matrix protein p17. p17 accumulates in lymph nodes of patients even when they are undergoing highly active antiretroviral therapy. p17 has been found to affect immune cells, and recent data showed that a variant p17, called S75X, induces cell growth by triggering MAPK/ERK and PI3K/AKT pathways. We tested the in vivo angiogenic activity of p17 by injecting it in Matrigel plugs in nude mice. Plugs were retrieved 7 days after injection, and assessed macroscopically, and by light and confocal microscopy. Our data revealed that both reference and S75X variant p17 promote angiogenesis and lymphangiogenesis in vivo. Our results suggest that the induction of angiogenesis and lymphangiogenesis by HIV-1 p17 may generate a favorable microenvironment that could trigger tumor growth and maintenance. Moreover, the presence of adipocytes infiltration observed at the histological level suggests a possible interplay between angiogenesis, lymphangiogenesis and adipogenesis. These findings offer new opportunities for the development of treatment strategies to combat HIV-related cancers.
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA Microbiology Section, Department of Molecular and Translational Medicine, University of Brescia, Brescia 25123, Italy.
Daniele
D
Basta
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA Department of Microbiology and Immunology, Baltimore, MD 21201, USA.
Olga
O
Latinovic
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Mark K
MK
Lafferty
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Lingling
L
Sun
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Joseph
J
Bryant
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA Department of Biochemistry and Molecular Biology, Baltimore, MD 21201, USA.
Wuyuan
W
Lu
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Francesca
F
Caccuri
Microbiology Section, Department of Molecular and Translational Medicine, University of Brescia, Brescia 25123, Italy.
Arnaldo
A
Caruso
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Robert
R
Gallo
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA Department of Microbiology and Immunology, Baltimore, MD 21201, USA Department of Molecular Medicine, University of Padova, 35123, Italy agarzinodemo@ihv.umaryland.edu alfredo.garzinodemo@unipd.it.
Alfredo
A
Garzino-Demo
D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D015488:HIV Antigens / Q000008:administration & dosage / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D042583:Lymphangiogenesis / Q000187:drug effects*; D008819:Mice, Nude; D008853:Microscopy; D009389:Neovascularization, Pathologic / Q000139:chemically induced*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage / Q000378:metabolism*
D015488:HIV Antigens; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1
HIV-1; adipogenesis; angiogienesis; lymphangiogenesis; lymphomagenesis; matrix protein