PMID- 10640428
OWN - NLM
STAT- MEDLINE
DCOM- 20000405
LR  - 20161124
IS  - 0014-4827 (Print)
IS  - 0014-4827 (Linking)
VI  - 254
IP  - 2
DP  - 2000 Feb 1
TI  - Activation of integrin alpha(V)beta(3) regulates cell adhesion and migration to
      bone sialoprotein.
PG  - 299-308
AB  - alpha(V)beta(3), a broadly distributed member of the integrin family of adhesion 
      receptors, has been implicated in a variety of physiological and
      pathophysiological events, including control of bone density, angiogenesis,
      apoptosis, tumor growth, and metastasis. Recently, it has been shown that
      activation of alpha(V)beta(3), its transition from a low- to a
      high-affinity/avidity state, influences its recognition of certain ligands. Bone 
      sialoprotein (BSP) is recognized as an important ligand for alpha(V)beta(3) in
      processes ranging from bone formation to the homing of metastatic tumor cells.
      Here, the influence of alpha(V)beta(3) activation on the adhesion and migration
      of relevant cells to BSP has been examined. Stimulation of lymphoblastoid,
      osteoblastoid, and human umbilical vein endothelial cells (HUVEC) with PMA or
      Mn(2+) markedly enhanced alpha(V)beta(3)-dependent adhesion to BSP.
      alpha(V)beta(3)-mediated migration of HUVEC or osteoblastic cells to BSP was
      substantially enhanced by stimulation, demonstrating that alpha(V)beta(3)
      activation enhances both adhesive and migratory responses. However, adhesion
      and/or migration of certain tumor cell lines, including M21 melanoma and MDA
      MB435 and SKBR3 breast carcinoma cell lines, to BSP was constitutively high and
      was not augmented by alpha(V)beta(3)-activating stimuli. Inhibitors of the
      intracellular signaling molecules, phosphatidylinositol 3-kinase with wortmannin,
      hsp90-dependent kinases with geldanamycin, and calpain with calpeptin, but not
      MAPKK with PD98059, reduced the high spontaneous adhesion and migration of the
      M21 cells to BSP, consistent with the constitutive activation of the receptor on 
      these tumor cells. These results indicate that the activation state of
      alpha(V)beta(3) can regulate cell migration and adhesion to BSP and, by
      extension, to other ligands of this receptor. The constitutive activation of
      alpha(V)beta(3) on neoplastic cells may contribute to tumor growth and metastatic
      potential.
CI  - Copyright 2000 Academic Press.
FAU - Byzova, T V
AU  - Byzova TV
AD  - Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Department of
      Molecular Cardiology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland,
      Ohio 44195, USA.
FAU - Kim, W
AU  - Kim W
FAU - Midura, R J
AU  - Midura RJ
FAU - Plow, E F
AU  - Plow EF
LA  - eng
GR  - HL54924/HL/NHLBI NIH HHS/United States
GR  - RR-00080/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (IBSP protein, human)
RN  - 0 (Integrin-Binding Sialoprotein)
RN  - 0 (Oligopeptides)
RN  - 0 (Receptors, Vitronectin)
RN  - 0 (Sialoglycoproteins)
RN  - 42Z2K6ZL8P (Manganese)
RN  - 78VO7F77PN (arginyl-glycyl-aspartic acid)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Cell Adhesion/drug effects/*physiology
MH  - Cell Line
MH  - Cells, Cultured
MH  - Chemotaxis/drug effects/*physiology
MH  - Endothelium, Vascular/cytology/*physiology
MH  - Humans
MH  - Integrin-Binding Sialoprotein
MH  - Lymphocytes/cytology/*physiology
MH  - Manganese/pharmacology
MH  - Melanoma
MH  - Oligopeptides/pharmacology
MH  - Osteoblasts/cytology/*physiology
MH  - Receptors, Vitronectin/*physiology
MH  - Sialoglycoproteins/*physiology
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Tumor Cells, Cultured
MH  - Umbilical Veins
EDAT- 2000/01/21 00:00
MHDA- 2000/01/21 00:01
CRDT- 2000/01/21 00:00
PHST- 2000/01/21 00:00 [pubmed]
PHST- 2000/01/21 00:01 [medline]
PHST- 2000/01/21 00:00 [entrez]
AID - 10.1006/excr.1999.4765 [doi]
AID - S0014-4827(99)94765-1 [pii]
PST - ppublish
SO  - Exp Cell Res. 2000 Feb 1;254(2):299-308. doi: 10.1006/excr.1999.4765.