title: Activation of VCAM-1 and its associated molecule CD44 leads to increased malignant potential of breast cancer cells.
abstract: VCAM-1 (CD106), a transmembrane glycoprotein, was first reported to play an important role in leukocyte adhesion, leukocyte transendothelial migration and cell activation by binding to integrin VLA-1 (α4β1). In the present study, we observed that VCAM-1 expression can be induced in many breast cancer epithelial cells by cytokine stimulation in vitro and its up-regulation directly correlated with advanced clinical breast cancer stage. We found that VCAM-1 over-expression in the NMuMG breast epithelial cells controls the epithelial and mesenchymal transition (EMT) program to increase cell motility rates and promote chemoresistance to doxorubicin and cisplatin in vitro. Conversely, in the established MDAMB231 metastatic breast cancer cell line, we confirmed that knockdown of endogenous VCAM-1 expression reduced cell proliferation and inhibited TGFβ1 or IL-6 mediated cell migration, and increased chemosensitivity. Furthermore, we demonstrated that knockdown of endogenous VCAM-1 expression in MDAMB231 cells reduced tumor formation in a SCID xenograft mouse model. Signaling studies showed that VCAM-1 physically associates with CD44 and enhances CD44 and ABCG2 expression. Our findings uncover the possible mechanism of VCAM-1 activation facilitating breast cancer progression, and suggest that targeting VCAM-1 is an attractive strategy for therapeutic intervention.
authors.affiliation: Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan. lovemessage1002@yahoo.com.tw.
authors.forename: Pei-Chen
authors.initials: PC
authors.lastname: Wang
authors.affiliation: Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan. inoursky@gmail.com.
authors.forename: Ching-Chieh
authors.initials: CC
authors.lastname: Weng
authors.affiliation: Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan. poo779779@gmail.com.
authors.forename: You-Syuan
authors.initials: YS
authors.lastname: Hou
authors.affiliation: Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan. chienfang1216@gmail.com.
authors.forename: Shu-Fang
authors.initials: SF
authors.lastname: Jian
authors.affiliation: Department of Research and Development, Eternal Chemical Co., Ltd., Kaohsiung 80778, Taiwan. CalvinFang@hotmail.com.
authors.forename: Kuan-Te
authors.initials: KT
authors.lastname: Fang
authors.affiliation: Department of Surgery, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung 80708, Taiwan. mifeho@kmu.edu.tw.
authors.forename: Ming-Feng
authors.initials: MF
authors.lastname: Hou
authors.affiliation: Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan. khcheng@faculty.nsysu.edu.tw.
authors.forename: Kuang-Hung
authors.initials: KH
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics* / Q000378:metabolism; D016513:Mice, SCID; D008875:Middle Aged; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D018960:Hyaluronan Receptors; D019010:Vascular Cell Adhesion Molecule-1; D004317:Doxorubicin; D002945:Cisplatin