INVESTIGADORES
ARREGUI Carlos Oscar
artículos
Título:
A phospholipase D and protein kinase C inhibitor blocks the spreading of murine mammary adenocarcinoma cells altering f-actin and beta1-integrin point contact distribution
Autor/es:
AGUIRRE GHISO, JULIO A; FARIAS, EDUARDO; ALONSO, DANIEL F; ARREGUI, CARLOS O; BAL DE KIER JOFFE, ELISA DORA; CARLOS OSCAR ARREGUI
Revista:
INTERNATIONAL JOURNAL OF CANCER. JOURNAL INTERNATIONAL DU CANCER.
Editorial:
Wiley-Liss
Referencias:
Año: 1997 vol. 72 p. 881 - 890
ISSN:
0020-7136
Resumen:
Spreading is a critical process involved in motility and
growth of tumor cells during the metastatic cascade. Focal
adhesion kinase, src-proteins and PKC have been reported to
participate in the regulation of cytoskeleton organization in
both normal and transformed cells during spreading. The role
of other signaling enzymes such as PLD and PAP has not been
studied during spreading in tumor cells. We now show that
the spreading of murine mammary adenocarcinoma LM3
cells was significantly reduced by n-butanol, a PLD and PKC
inhibitor, with a maximal inhibition of 54% (p F 0.001) in both
the presence and absence of serum, as measured by phasecontrast
microscopy. PMA only stimulated cell spreading
over the control in the absence of serum and n-butanol
inhibition was completely reversed by PMA treatment in
both conditions. PA, the product of PLD activity, stimulated
LM3 cell spreading and the same effect was observed with
staurosporine. Spreading was enhanced when cells were
seeded on collagen-IV- or fibronectin-coated surfaces and
n-butanol could inhibit both integrin-derived signals. Cell
spreading inhibition correlated with the absence of f-actin
bundles and fewer b1-integrin point contacts as determined
by double immunofluorescence microscopy. In addition, nbutanol
inhibited the proliferation of LM3 cells in the presence
of serum (p F 0.01). These results suggest that b1-
integrin and f-actin/point contact assembly, involved in
spreading and proliferation, require the participation of PLDPKC
regulatory pathways in LM3 cells.
integrin and f-actin/point contact assembly, involved in
spreading and proliferation, require the participation of PLDPKC
regulatory pathways in LM3 cells.
p
by double immunofluorescence microscopy. In addition, nbutanol
inhibited the proliferation of LM3 cells in the presence
of serum (p F 0.01). These results suggest that b1-
integrin and f-actin/point contact assembly, involved in
spreading and proliferation, require the participation of PLDPKC
regulatory pathways in LM3 cells.
integrin and f-actin/point contact assembly, involved in
spreading and proliferation, require the participation of PLDPKC
regulatory pathways in LM3 cells.
p
the presence and absence of serum, as measured by phasecontrast
microscopy. PMA only stimulated cell spreading
over the control in the absence of serum and n-butanol
inhibition was completely reversed by PMA treatment in
both conditions. PA, the product of PLD activity, stimulated
LM3 cell spreading and the same effect was observed with
staurosporine. Spreading was enhanced when cells were
seeded on collagen-IV- or fibronectin-coated surfaces and
n-butanol could inhibit both integrin-derived signals. Cell
spreading inhibition correlated with the absence of f-actin
bundles and fewer b1-integrin point contacts as determined
by double immunofluorescence microscopy. In addition, nbutanol
inhibited the proliferation of LM3 cells in the presence
of serum (p F 0.01). These results suggest that b1-
integrin and f-actin/point contact assembly, involved in
spreading and proliferation, require the participation of PLDPKC
regulatory pathways in LM3 cells.
integrin and f-actin/point contact assembly, involved in
spreading and proliferation, require the participation of PLDPKC
regulatory pathways in LM3 cells.
p
by double immunofluorescence microscopy. In addition, nbutanol
inhibited the proliferation of LM3 cells in the presence
of serum (p F 0.01). These results suggest that b1-
integrin and f-actin/point contact assembly, involved in
spreading and proliferation, require the participation of PLDPKC
regulatory pathways in LM3 cells.
integrin and f-actin/point contact assembly, involved in
spreading and proliferation, require the participation of PLDPKC
regulatory pathways in LM3 cells.
p
p F 0.001) in both
the presence and absence of serum, as measured by phasecontrast
microscopy. PMA only stimulated cell spreading
over the control in the absence of serum and n-butanol
inhibition was completely reversed by PMA treatment in
both conditions. PA, the product of PLD activity, stimulated
LM3 cell spreading and the same effect was observed with
staurosporine. Spreading was enhanced when cells were
seeded on collagen-IV- or fibronectin-coated surfaces and
n-butanol could inhibit both integrin-derived signals. Cell
spreading inhibition correlated with the absence of f-actin
bundles and fewer b1-integrin point contacts as determined
by double immunofluorescence microscopy. In addition, nbutanol
inhibited the proliferation of LM3 cells in the presence
of serum (p F 0.01). These results suggest that b1-
integrin and f-actin/point contact assembly, involved in
spreading and proliferation, require the participation of PLDPKC
regulatory pathways in LM3 cells.
integrin and f-actin/point contact assembly, involved in
spreading and proliferation, require the participation of PLDPKC
regulatory pathways in LM3 cells.
p
by double immunofluorescence microscopy. In addition, nbutanol
inhibited the proliferation of LM3 cells in the presence
of serum (p F 0.01). These results suggest that b1-
integrin and f-actin/point contact assembly, involved in
spreading and proliferation, require the participation of PLDPKC
regulatory pathways in LM3 cells.
integrin and f-actin/point contact assembly, involved in
spreading and proliferation, require the participation of PLDPKC
regulatory pathways in LM3 cells.
p
b1-integrin point contacts as determined
by double immunofluorescence microscopy. In addition, nbutanol
inhibited the proliferation of LM3 cells in the presence
of serum (p F 0.01). These results suggest that b1-
integrin and f-actin/point contact assembly, involved in
spreading and proliferation, require the participation of PLDPKC
regulatory pathways in LM3 cells.
integrin and f-actin/point contact assembly, involved in
spreading and proliferation, require the participation of PLDPKC
regulatory pathways in LM3 cells.
p F 0.01). These results suggest that b1-
integrin and f-actin/point contact assembly, involved in
spreading and proliferation, require the participation of PLDPKC
regulatory pathways in LM3 cells.