title: Lymphatic endothelial cells support tumor growth in breast cancer.
abstract: Tumor lymphatic vessels (LV) serve as a conduit of tumor cell dissemination, due to their leaky nature and secretion of tumor-recruiting factors. Though lymphatic endothelial cells (LEC) lining the LV express distinct factors (also called lymphangiocrine factors), these factors and their roles in the tumor microenvironment are not well understood. Here we employ LEC, microvascular endothelial cells (MEC), and human umbilical vein endothelial cells (HUVEC) cultured in triple-negative MDA-MB-231 tumor-conditioned media (TCM) to determine the factors that may be secreted by various EC in the MDA-MB-231 breast tumor. These factors will serve as endothelium derived signaling molecules in the tumor microenvironment. We co-injected these EC with MDA-MB-231 breast cancer cells into animals and showed that LEC support tumor growth, HUVEC have no significant effect on tumor growth, whereas MEC suppress it. Focusing on LEC-mediated tumor growth, we discovered that TCM-treated LEC ('tumor-educated LEC') secrete high amounts of EGF and PDGF-BB, compared to normal LEC. LEC-secreted EGF promotes tumor cell proliferation. LEC-secreted PDGF-BB induces pericyte infiltration and angiogenesis. These lymphangiocrine factors may support tumor growth in the tumor microenvironment. This study shows that LV serve a novel role in the tumor microenvironment apart from their classical role as conduits of metastasis.
authors: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States.
authors: Esak
authors: E
authors: Lee
authors: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States.
authors: Niranjan B
authors: NB
authors: Pandey
authors: 1] Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States [2] Department of Oncology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, United States.
authors: Aleksander S
authors: AS
authors: Popel
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D042361:Mammary Glands, Human / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D055806:Microvessels / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics / Q000378:metabolism; D047368:Tumor Burden
chemical_list: D017077:Culture Media, Conditioned; D020574:Proto-Oncogene Proteins c-sis