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Dr. Lyden's laboratory then went on to show that growth factors secreted by the primary tumor prime certain tissues for tumor cell engraftment (Nature, 2005). His laboratory defined the concept of the "pre-metastatic niche," showing that in response to tumor-secreted factors, tumor-associated cells such as hematopoietic progenitor cells are recruited to future metastatic niches creating an environment that is conducive for tumor cell adhesion and invasion. At the pre-metastatic niche, newly recruited myeloid cells collaborate with other cell types residing in the tissue parenchyma. Together, these cells provide a platform of chemokines (such as S100 family members), growth factors, matrix-degrading enzymes (MMP9) and adhesion molecules (fibronectin and laminin), thereby accelerating assembly of the metastatic lesion. This model suggests that it may be beneficial for systemic therapies targeted to the metastatic microenvironment to be used early, perhaps even as an adjunct to the initial treatment of the primary tumor (Nature Reviews Cancer, 2009; Nature Reviews Cancer, 2015). Finally, there is the implication that treatments may need to be tailored to each stage of metastatic progression: pre-metastatic, micrometastatic and macrometastatic as well as to specific metastatic niches (lung, liver, brain, bone marrow). Dr. Lyden's team investigation of tumor-secreted factors that mediate the crosstalk between tumors and cells in the remote metastatic microenvironment led to his discovery that tumor-secreted microvesicles, known as exosomes, initiate pre-metastatic niche formation by educating bone marrow progenitor cells towards a pro-angiogenic phenotype, thus supporting a metastatic phenotype (Nature Medicine, 2012).
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Yujie Huang,Caitlin Hoffman,Prajwal Rajappa, Joon-Hyung Kim, Wenhuo Hu,Jason Huse,Zhongshu Tang,Xuri Li, Babette Weksler,Jacqueline Bromberg,David C. Lyden, Jeffrey P. Greenfield
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Shuchen Liu,Alberto Benito-Martin,Fanny A Pelissier Vatter, Sarah Z Hanif,Catherine Liu,Priya Bhardwaj,Praveen Sethupathy, Alaa R Farghli,Phoebe Piloco,Paul Paik,Malik Mushannen,David M Otterburn,
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