title: Mena invasive (MenaINV) promotes multicellular streaming motility and transendothelial migration in a mouse model of breast cancer.
abstract: We have shown previously that distinct Mena isoforms are expressed in invasive and migratory tumor cells in vivo and that the invasion isoform (Mena(INV)) potentiates carcinoma cell metastasis in murine models of breast cancer. However, the specific step of metastatic progression affected by this isoform and the effects on metastasis of the Mena11a isoform, expressed in primary tumor cells, are largely unknown. Here, we provide evidence that elevated Mena(INV) increases coordinated streaming motility, and enhances transendothelial migration and intravasation of tumor cells. We demonstrate that promotion of these early stages of metastasis by Mena(INV) is dependent on a macrophage-tumor cell paracrine loop. Our studies also show that increased Mena11a expression correlates with decreased expression of colony-stimulating factor 1 and a dramatically decreased ability to participate in paracrine-mediated invasion and intravasation. Our results illustrate the importance of paracrine-mediated cell streaming and intravasation on tumor cell dissemination, and demonstrate that the relative abundance of Mena(INV) and Mena11a helps to regulate these key stages of metastatic progression in breast cancer cells.
authors.affiliation: Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. evanthia.roussos@med.einstein.yu.edu
authors.forename: Evanthia T
authors.initials: ET
authors.lastname: Roussos
authors.forename: Michele
authors.initials: M
authors.lastname: Balsamo
authors.forename: Shannon K
authors.initials: SK
authors.lastname: Alford
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Wyckoff
authors.forename: Bojana
authors.initials: B
authors.lastname: Gligorijevic
authors.forename: Yarong
authors.initials: Y
authors.lastname: Wang
authors.forename: Maria
authors.initials: M
authors.lastname: Pozzuto
authors.forename: Robert
authors.initials: R
authors.lastname: Stobezki
authors.forename: Sumanta
authors.initials: S
authors.lastname: Goswami
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Segall
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Lauffenburger
authors.forename: Anne R
authors.initials: AR
authors.lastname: Bresnick
authors.forename: Frank B
authors.initials: FB
authors.lastname: Gertler
authors.forename: John S
authors.initials: JS
authors.lastname: Condeelis
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005260:Female; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D008840:Microfilament Proteins; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D057705:Transendothelial and Transepithelial Migration
chemical_list: D003598:Cytoskeletal Proteins; C102176:Enah protein, mouse; D008840:Microfilament Proteins; D020033:Protein Isoforms; D016173:Macrophage Colony-Stimulating Factor