title: By activating matrix metalloproteinase-7, shear stress promotes chondrosarcoma cell motility, invasion and lung colonization.
abstract: Interstitial fluid flow and associated shear stress are relevant mechanical signals in cartilage and bone (patho)physiology. However, their effects on chondrosarcoma cell motility, invasion and metastasis have yet to be delineated. Using human SW1353, HS.819.T and CH2879 chondrosarcoma cell lines as model systems, we found that fluid shear stress induces the accumulation of cyclic AMP (cAMP) and interleukin-1β (IL-1β), which in turn markedly enhance chondrosarcoma cell motility and invasion via the induction of matrix metalloproteinase-7 (MMP-7). Specifically, shear-induced cAMP and IL-1β activate PI3-K, ERK1/2 and p38 signaling pathways, which lead to the synthesis of MMP-7 via transactivating NF-κB and c-Jun in human chondrosarcoma cells. Importantly, MMP-7 upregulation in response to shear stress exposure has the ability to promote lung colonization of chondrosarcomas in vivo. These findings offer a better understanding of the mechanisms underlying MMP-7 activation in shear-stimulated chondrosarcoma cells, and provide insights on designing new therapeutic strategies to interfere with chondrosarcoma invasion and metastasis.
authors.affiliation: College of Life and Health Sciences, Northeastern University, Shenyang 110819, P. R. China.
authors.forename: Pei-Pei
authors.initials: PP
authors.lastname: Guan
authors.affiliation: College of Life and Health Sciences, Northeastern University, Shenyang 110819, P. R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.affiliation: College of Life and Health Sciences, Northeastern University, Shenyang 110819, P. R. China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Guo
authors.affiliation: College of Life and Health Sciences, Northeastern University, Shenyang 110819, P. R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Life and Health Sciences, Northeastern University, Shenyang 110819, P. R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: College of Life and Health Sciences, Northeastern University, Shenyang 110819, P. R. China.|Neural Plasticity and Repair Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Sciences, Lund University, Lund 22184, Sweden.
authors.forename: Jia-Yi
authors.initials: JY
authors.lastname: Li
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, United States of America.|Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, United States of America.|Johns Hopkins Institute for NanoBioTechnology, The Johns Hopkins University, Baltimore, Maryland 21218, United States of America.|Johns Hopkins Physical Sciences-Oncology Center, Center of Cancer Nanotechonology Excellence, The Johns Hopkins University, Baltimore, Maryland 21218, United States of America.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Konstantopoulos
authors.affiliation: College of Life and Health Sciences, Northeastern University, Shenyang 110819, P. R. China.
authors.forename: Zhan-You
authors.initials: ZY
authors.lastname: Wang
authors.affiliation: College of Life and Health Sciences, Northeastern University, Shenyang 110819, P. R. China.
authors.forename: Pu
authors.initials: P
authors.lastname: Wang
mesh_terms: D001859:Bone Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002813:Chondrosarcoma / Q000473:pathology*; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008175:Lung Neoplasms / Q000556:secondary*; D020935:MAP Kinase Signaling System; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D013314:Stress, Mechanical; D013312:Stress, Physiological; D015533:Transcriptional Activation; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C508585:IL1B protein, human; D053583:Interleukin-1beta; D016328:NF-kappa B; D012333:RNA, Messenger; D000242:Cyclic AMP; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7
keywords: chondrosarcoma metastasis; cyclic AMP; fluid shear stress; interleukin-1beta; matrix metalloproteinase 7
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