The authors investigated molecular mechanisms that altered the growth and metabolism of isolated lymphatic endothelial cells exposed to prolonged pathologically elevated lymph flow in vivo within the anatomic and physiologic context of a large animal model of congenital heart disease with increased pulmonary blood flow using in vitro approaches.
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Boehme, J. T., Morris, C. J., Chiacchia, S. R., Gong, W., Wu, K. Y., Kameny, R. J., Raff, G. W., Fineman, J. R., Maltepe, E., & Datar, S. A. (2021). HIF-1α promotes cellular growth in lymphatic endothelial cells exposed to chronically elevated pulmonary lymph flow. Scientific Reports, 11(1), 1468. https://doi.org/10.1038/s41598-020-80882-1 Cite
The authors established a novel zebrafish transgenic line expressing eGFP under the control of part of the zebrafish Basic Leucine Zipper ATF‐Like Transcription Factor 3 (batf3) promoter. Spatiotemporal examination of Tg(batf3MIN:eGFP) transgenic fish revealed a typical lymphatic expression pattern, which does not perfectly recapitulate the expression pattern of existing lymphatic endothelial cell transgenic lines.
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Scientists report a mechanistic model via which cervical cancer-secreted, exosome-encapsulated miR-1468-5p promoted lymphatic PD-L1 upregulation and lymphangiogenesis to impair T cell immunity.
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Zhou, C., Wei, W., Ma, J., Yang, Y., Liang, L., Zhang, Y., Wang, Z., Chen, X., Huang, L., Wang, W., & Wu, S. (2020). Cancer-secreted exosomal miR-1468-5p promotes tumor immune escape via the immunosuppressive reprogramming of lymphatic vessels. Molecular Therapy, 0(0). https://doi.org/10.1016/j.ymthe.2020.12.034 Cite
Culturing primary mouse cardiomyocytes in lymphatic endothelial cells (LEC)-conditioned medium increased cardiomyocyte proliferation and survival, indicating that LECs produce lymphoangiocrine signals that control cardiomyocyte homeostasis.
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Liu, X., De la Cruz, E., Gu, X., Balint, L., Oxendine-Burns, M., Terrones, T., Ma, W., Kuo, H.-H., Lantz, C., Bansal, T., Thorp, E., Burridge, P., Jakus, Z., Herz, J., Cleaver, O., Torres, M., & Oliver, G. (2020). Lymphoangiocrine signals promote cardiac growth and repair. Nature, 1–7. https://doi.org/10.1038/s41586-020-2998-x Cite
The authors analyzed metabolites inside lymphatic endothelial cells (LECs) in co-culture with MCF-7, MDA-MB-231, and SK-BR-3 breast cancer cell lines using 1H nuclear magnetic resonance metabolomics, Seahorse, and the spatial distribution of metabolic co-enzymes using optical redox ratio imaging to describe breast cancer-LEC metabolic crosstalk.
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Acevedo-Acevedo, S., Millar, D. C., Simmons, A. D., Favreau, P., Cobra, P. F., Skala, M., & Palecek, S. P. (2020). Metabolomics revealed the influence of breast cancer on lymphatic endothelial cell metabolism, metabolic crosstalk, and lymphangiogenic signaling in co-culture. Scientific Reports, 10(1), 21244. https://doi.org/10.1038/s41598-020-76394-7 Cite
Investigators evaluated, in vitro, the potential paracrine effect of human adipose-derived stem cells to promote lymphangiogenesis in lymphatic endothelial cells isolated from rat diaphragmatic lymphatic vessels.
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Investigators describe the features of tumor microenvironment within the primitive breast cancer, throughout its evolution and spread into the main metastatic sites.
[International Journal of Molecular Sciences]
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Zarrilli, G., Businello, G., Dieci, M. V., Paccagnella, S., Carraro, V., Cappellesso, R., Miglietta, F., Griguolo, G., Guarneri, V., Lo Mele, M., & Fassan, M. (2020). The Tumor Microenvironment of Primitive and Metastatic Breast Cancer: Implications for Novel Therapeutic Strategies. International Journal of Molecular Sciences, 21(21), 8102. https://doi.org/10.3390/ijms21218102 Cite
The glycolysis index, including glucose uptake, ATP and lactate production stayed at a relatively high level in human dermal lymphatic endothelial cells (HDLECs) compared with HUVECS, while inhibition of PKM2 by shikinon or PKM2 knockdown could significantly suppress glycolysis, migration, tubular formation, and invasion of HDLECs.
[American Journal of Pathology]
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Jiang, H., Zou, Y., Zhao, J., Li, X., Yang, S., Zhou, X., Mou, D., Zhong, W., & Cai, Y. (2020). Pyruvate kinase M2 mediates the glycolysis in the lymphatic endothelial cells and its potential relation to the progression of lymphatic malformations. The American Journal of Pathology, 0(0). https://doi.org/10.1016/j.ajpath.2020.10.003 Cite
The authors established a GEMM fragment-based tumor model uniquely sustaining a functional network of intratumoral lymphatics that facilitated seeding of fatal peripheral metastases.
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Gengenbacher, N., Singhal, M., Mogler, C., Hai, L., Milde, L., Pari, A. A. A., Besemfelder, E., Fricke, C., Baumann, D., Gehrs, S., Utikal, J., Felcht, M., Hu, J., Schlesner, M., Offringa, R., Chintharlapalli, S., & Augustin, H. G. (2020). Timed Ang2-targeted therapy identifies the Angiopoietin-Tie pathway as key regulator of fatal lymphogenous metastasis. Cancer Discovery. https://doi.org/10.1158/2159-8290.CD-20-0122 Cite
Investigators revealed a new mechanism by which tumor exposed-lymphatic endothelial cells (teLEC) exert mitogenic effects on tumor cells. Their conclusions were supported by morphological and molecular changes induced in teLEC that in turn enhance cancer cell invasion in 3D cultures and tumor cell proliferation in vivo.
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The authors review recent findings describing new origins of lymphatic endothelial cells during embryonic development and discuss their relevance to cancer lymphangiogenesis.
[Frontiers in Physiology]