Mechanical suppression of breast cancer cell invasion and paracrine signaling to osteoclasts requires nucleo-cytoskeletal connectivity  

作　　者：Xin Yi Laura E.Wright Gabriel M.Pagnotti Gunes Uzer Katherine M.Powell Joseph M.Wallace Uma Sankar Clinton T.Rubin Khalid Mohammad Theresa A.Guise William R.Thompson 

机构地区：[1]Department of Physical Therapy,School of Health and Rehabilitation Sciences,Indiana University,Indianapolis,IN 46202,USA [2]Department of Medicine,Division of Endocrinology,School of Medicine,Indiana University,Indianapolis,IN 46202,USA [3]Department of Mechanical and Biomedical Engineering,Boise State University,Boise,ID 83725,USA [4]Department of Biomedical Engineering,Purdue School of Engineering and Technology,Purdue University,Indianapolis,IN 46202,USA [5]Department of Anatomy&Cell Biology,Indiana University,Indianapolis,IN 46202,USA [6]Department of Biomedical Engineering,Stony Brook University,Stony Brook,NY 11794,USA

出　　处：《Bone Research》2020年第4期393-405,共13页骨研究（英文版）

基　　金：Department of Defense BC150678P1(WRT),NIH AR069943-01(WRT),NIH AR068332(US),and Department of Defense BC150678(TAG).

摘　　要：Exercise benefits the musculoskeletal system and reduces the effects of cancer.The effects of exercise are multifactorial,where metabolic changes and tissue adaptation influence outcomes.Mechanical signals,a principal component of exercise,are anabolic to the musculoskeletal system and restrict cancer progression.We examined the mechanisms through which cancer cells sense and respond to low-magnitude mechanical signals introduced in the form of vibration.Low-magnitude,high-frequency vibration was applied to human breast cancer cells in the form of low-intensity vibration(LIV).LIV decreased matrix invasion and impaired secretion of osteolytic factors PTHLH,IL-11,and RANKL.Furthermore,paracrine signals from mechanically stimulated cancer cells,reduced osteoclast differentiation and resorptive capacity.Disconnecting the nucleus by knockdown of SUN1 and SUN2 impaired LIV-mediated suppression of invasion and osteolytic factor secretion.LIV increased cell stiffness;an effect dependent on the LINC complex.These data show that mechanical vibration reduces the metastatic potential of human breast cancer cells,where the nucleus serves as a mechanosensory apparatus to alter cell structure and intercellular signaling.

关 键 词：INVASION IMPAIRED SKELETAL 

分 类 号：R737.9[医药卫生—肿瘤]