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PMID: 21680800 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Release of angiogenesis regulatory proteins from platelet alpha granules: modulation of physiologic and pathologic angiogenesis.

Blood ·Vol. 118 ·No. 5 ·2011-08-04 ·Pages 1359-69

Battinelli EM, Markens BA, Italiano JE

Abstract

An association between platelets, angiogenesis, and cancer has long been recognized, but the mechanisms linking them remains unclear. Platelets regulate new blood vessel growth through numerous stimulators and inhibitors of angiogenesis by several pathways, including differential exocytosis of angiogenesis regulators. Herein, we investigated the differential release of angiogenesis stimulators and inhibitors from platelets. Activation of human platelets with adenosine diphosphate (ADP) stimulated the release of VEGF, but not endostatin whereas, thromboxane A(2) (TXA(2)) released endostatin but not VEGF. Platelet releasates generated by activation with ADP promoted migration and formation of capillary structures by human umbilical vein endothelial cells (HUV-EC-Cs) in in vitro angiogenesis models. Conversely, TXA(2)-stimulated platelet releasate inhibited migration and formation of capillary structures. Because tumor growth beyond 1-2 mm(3) is angiogenesis-dependent, we hypothesized that cancer cells preferentially stimulate platelets to secrete their pro-angiogenic payload. In support of this, the breast cancer cell line MCF-7 stimulated secretion of VEGF and a pro-angiogenic releasate from platelets. Furthermore, the antiplatelet agent aspirin inhibited platelet-mediated angiogenesis after exposure to ADP or MCF-7 cells providing a potential mechanism for how aspirin may impact malignancy. Manipulation of differentially mediated release of angiogenic factors from platelets may provide a new modality for cancer treatment.

MeSH Terms
Adenosine Diphosphate/pharmacology Angiogenesis Modulating Agents/metabolism,pharmacology Aspirin/pharmacology Blood Platelets/metabolism Breast Neoplasms/pathology Carcinoma/pathology Cells, Cultured Endostatins/metabolism,pharmacology Endothelial Cells/drug effects,metabolism,physiology Female Humans Models, Biological Neovascularization, Pathologic/etiology,prevention & control Neovascularization, Physiologic/drug effects Secretory Vesicles/drug effects,metabolism Thromboxane A2/pharmacology Vascular Endothelial Growth Factor A/metabolism,pharmacology
Chemicals
Angiogenesis Modulating Agents Endostatins Vascular Endothelial Growth Factor A Thromboxane A2 Adenosine Diphosphate Aspirin
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Battinelli Elisabeth M
Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. ebattinelli@partners.org
Markens Beth A
Italiano Joseph E
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
1528-0020
DOI
10.1182/blood-2011-02-334524
Email
ebattinelli@partners.org
Published
2011-08-04
Epub
2011-00-16
Pages
1359-69
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC3152500
Subset
IM
Grants
NHLBI NIH HHS · K08 HL097070 · United States
NCI NIH HHS · P01 CA045548 · United States
NHLBI NIH HHS · K08HL097070 · United States
NCI NIH HHS · P01 CA045548-21 · United States
External Links
PubMed source DOI: 10.1182/blood-2011-02-334524 PMC Full Text View journal details
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