**Acknowledgements**

*4.4.3. Lymphatic vasculature in the mammary gland*

108 Stromal Cells - Structure, Function, and Therapeutic Implications

VEGF-C [93].

*4.4.4. Summary*

gland (**Figure 2**).

pounds to provide oxygen, remove CO<sup>2</sup>

When describing the vasculature present within the structure of the mammary gland, one needs to mention also the lymphatic vasculature, which plays a distinct role in the gland's function. Lymphatic vessels serve to return the interstitial protein-rich fluid to the bloodstream, absorb dietary fats and fat-soluble vitamins from the digestive tract, and traffic the immune cells to the site of their physiological destination, as well as at the time of infection [91]. Very little is known about the course of lymphatic vessel formation during mammogenesis. Betterman and co-workers described the process of lymphangiogenesis during the postnatal development of the mouse mammary gland [91]. The authors showed that lymphatic vessels share an intimate spatial association with epithelial ducts and large blood vessels. Lymphatic vessels were observed to encircle epithelial ducts in the mammary glands of virgin and pregnant mice; however, these vessels were not dispersed throughout the stroma and were excluded from alveoli during pregnancy [91]. In contrast, lymphatic vessels in the rat mammary gland were found throughout the interlobular connective tissue and in close association with the alveoli during pregnancy, pointing at substantial interspecies differences [92]. The results of the study performed by Betterman and coworkers [91] have indicated that myoepithelial cells are the source of prolymphangiogenic growth factors, such as VEGF-C and VEGF-D, that drive the expansion of lymphatic vasculature. Interestingly, the lymphatic vessels were not observed in close proximity to alveoli in the pregnant and lactating murine mammary glands. This phenomenon could be caused by insufficient prolymphangiogenic stimuli originating from myoepithelial cells which form a discontinuous sheath around the secretory MECs of the alveoli. Alternatively, the absence of lymphatic vessels could result from repulsive bioactive compounds secreted by the alveolar epithelium [91]. Among the considered molecules showing possible properties of repelling the lymphatic vascular growth is soluble VEGF receptor 2 (sVEGFR-2), which was shown to maintain the lymphatic state of cornea by sequestering endogenous

Mammary vasculature supports three aspects of mammary gland physiology: (1) capillary endothelial cells form a semipermeable barrier that facilitates the exchange of serum com-

energy metabolism; (2) vascular endothelium provides a high rate of transfer of blood-derived components, such as glucose and amino acids for efficient synthesis of milk; (3) it also plays a significant role in orchestrating host defense to infectious pathogens, which is especially important in extensively active bovine mammary gland producing milk volumes that exceed the nutritional requirements of the offspring. Still, the intricacy of the epithelial-endothelial interactions and their impact on mammary gland development remain largely undiscovered. Further research is needed to gain more knowledge about the role of endothelial cells in the complex interactions between the stromal and epithelial compartments of the mammary

, and transfer solutes and macromolecules for cellular

This work was supported by a grant no: KNOW2015/CB/PRO1/21 from KNOW (Leading National Research Centre) Scientific Consortium "Healthy Animal—Safe Food" (decision of Ministry of Science and Higher Education No. 05-1/KNOW2/2015). Publication of this chapter was funded by KNOW (Leading National Research Centre) Scientific Consortium "Healthy Animal—Safe Food", decision of Ministry of Science and Higher Education No. 05-1/KNOW2/2015.
