Poster Presentation 6th Australian Health and Medical Research Congress 2012

Dynamic remodelling of the lymphatic vasculature during postnatal mouse mammary gland morphogenesis is mediated via epithelial-derived lymphangiogenic stimuli. (#323)

Kelly L Betterman 1 2 , Sophie Paquet-Fifield 3 , Marie-Liesse Asselin-Labat 4 , Jane E Visvader 4 5 , Lisa M Butler 2 6 , Steven A Stacker 3 7 , Marc G Achen 3 7 , Natasha L Harvey 1 2
  1. Centre for Cancer Biology, SA Pathology, Adelaide, SA, Australia
  2. Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia
  3. Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
  4. The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
  5. The University of Melbourne, Parkville, Victoria, Australia
  6. Dame Roma Mitchell Cancer Research Laboratories, Hanson Institute, SA Pathology, Adelaide, SA, Australia
  7. Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia

Lymphatic vessels are of fundamental importance to breast cancer patients. Lymphatic vessels not only provide a key route of transport for the metastasis of breast cancer cells, but their damage during axillary lymph node resection results in secondary lymphoedema. Mammary tissue undergoes major, dynamic remodelling in response to hormonal signals during puberty, pregnancy, lactation and the oestrous cycle. The morphogenesis of mammary gland epithelial and stromal components is accompanied by dynamic growth and regression of the blood vasculature. While blood vascular remodelling during mammary gland morphogenesis has been well documented, little is known about the growth and development of lymphatic vessels in this tissue. We have developed a three dimensional imaging approach to investigate lymphatic vessel growth and patterning during mouse mammary gland morphogenesis and reveal that lymphatic vessels in the postnatal mouse mammary gland share an intimate spatial association with epithelial ducts and large blood vessels. Moreover, we demonstrate that the lymphatic vasculature is dynamically remodelled during mammary gland morphogenesis; growth of the lymphatic vessel network accompanies expansion of the mammary epithelial tree during pregnancy and is followed by regression during involution. We demonstrate that epithelial cells, in particular myoepithelial cells, are a rich source of pro-lymphangiogenic stimuli including VEGF-C, VEGF-D and FGF2, and that expression of these growth factors is temporally regulated during mammary gland morphogenesis. Our work sheds new light on the mechanisms by which the lymphatic vasculature is patterned during development, reveals that the mammary epithelial tree provides a key source of growth factors driving lymphangiogenesis during mammary gland morphogenesis and provides a new explanation for the propensity of metastatic breast tumour cells to gain access to the lymphatic vasculature.