The lymphatic microcirculation is a key component of metastatic spread providing a pathway for cancer celldissemination, and the endothelium seems to enhance or promote the invasiveness of certain cancer cells.Furthermore, some tumors secrete lymphangiogenic growth factors acting on the lymphatic vasculature tofacilitate metastasis. This study, based on 875 ultrastructural serial sections and 9 three-dimensionalreconstructions of 28 initial lymphatics, clarify the transmigration mechanism of cancer cells from theextravascular matrix to the lumen of initial lymphatics. The lymphatic identification and distribution wereassessed by transmission electron microscopy and immunohistochemistry (D2-40 and LYVE-1 markers) inexperimental murine tumor mass (T84 adenocarcinoma, B16 melanoma, and transgenic prostateadenocarcinoma).The initial lymphatics were detectable in peritumoral connective tissue showing an endothelium lacking ofcontinuous basal membrane. Twenty-nine invasive phenotype cancer cells were detected to migrate fromthe extravascular matrix of peritumoral connective tissue towards the initial lymphatic taking firm adhesionwith the abluminal endothelial wall. The ultrastructural feature analysis and their reconstruction showed acancer cell passage through the interdigitating and overlapping interendothelial contacts of the lymphaticvessels, without evidences of endothelial barrier degradation indicating the plasticity of endothelial cells.This study provide concrete contribution on the mechanism underlying the interactions between cancer celland lymphatic endothelium, demonstrating a cancer cell transmigratory pathway. The discovery of themolecular mechanisms controlling these interactions could lead to new therapeutic strategies to reducemetastatic diffusion.
Lingua originaleEnglish
Numero di pagine1
Stato di pubblicazionePublished - 2014


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