Autocrine human growth hormone promotes tumor angiogenesis in mammary carcinoma.
Accumulating literature implicates pathological angiogenesis and lymphangiogenesis as playing key roles in tumor progression. Autocrine human growth hormone (hGH) is a wild-type orthotopically expressed oncogene for the human mammary epithelial cell. Herein we demonstrate that autocrine hGH expression in the human mammary carcinoma cell line MCF-7 stimulated the survival, proliferation, migration, and invasion of a human microvascular endothelial cell line (HMEC-1). Autocrine/paracrine hGH secreted from mammary carcinoma cells also promoted HMEC-1 in vitro tube formation as a consequence of increased vascular endothelial growth factor-A (VEGF-A) expression. Semiquantitative RT-PCR analysis demonstrated that HMEC-1 cells express both hGH and the hGH receptor (hGHR). Functional antagonism of HMEC-1-derived hGH reduced HMEC-1 survival, proliferation, migration/invasion, and tube formation in vitro. Autocrine/paracrine hGH secreted by mammary carcinoma cells increased tumor blood and lymphatic microvessel density in a xenograft model of human mammary carcinoma. Autocrine hGH is therefore a potential master regulator of tumor neovascularization, coordinating two critical processes in mammary neoplastic progression, angiogenesis and lymphangiogenesis. Consideration of hGH antagonism to inhibit angiogenic processes in mammary carcinoma is therefore warranted.
Brunet-Dunand
Severine E
SE
Liggins Institute, University of Auckland, Private Bag, Auckland, New Zealand.
Vouyovitch
Cecile
C
Araneda
Silvia
S
Pandey
Vijay
V
Vidal
Laurent J-P
LJ
Print
Cristin
C
Mertani
Hichem C
HC
Lobie
Peter E
PE
Perry
Jo K
JK
D019898:Autocrine Communication / Q000502:physiology; D001943:Breast Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002277:Carcinoma / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019382:Human Growth Hormone / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D042583:Lymphangiogenesis / Q000187:drug effects / Q000235:genetics; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000139:chemically induced* / Q000235:genetics; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; D042461:Vascular Endothelial Growth Factor A; D019382:Human Growth Hormone; C051815:somatotropin-binding protein