Abstract:
Accumulating literature implicates pathological angiogenesis and lymphangiogenesis as playing key roles in tumour 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 VEGF-A expression. Semi-quantitative 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 tumour blood and lymphatic microvessel density in a xenograft model of human mammary carcinoma. Autocrine hGH is therefore a potential master regulator of tumour neovascularisation, 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.
