INVESTIGADORES
PITOSSI Fernando Juan
artículos
Título:
Secreted Protein Acidic and Rich in Cysteine Produced by Human Melanoma Cells Modulates Polymorphonuclear Leukocyte Recruitment and Antitumor Cytotoxic Capacity
Autor/es:
MARIANO J. ALVAREZ; FEDERICO PRADA; M. FERNANDA LEDDA; ALICIA I. BRAVO; VIVIANA P. LUTZKY; SORAYA ADRIS; NELSON DI PAOLO; CECILIA CARBONE; LEONARDO FAINBOIM; FERNANDO PITOSSI; H. EDUARDO CHULUYAN; OSVALDO PODHAJCER
Revista:
CANCER RESEARCH
Editorial:
AMER ASSOC CANCER RESEARCH
Referencias:
Año: 2005 vol. 65 p. 5123 - 5132
ISSN:
0008-5472
Resumen:
The expression of secreted protein acidic and rich in cysteine
(SPARC) has been associated with the malignant progression
of different types of human cancer. SPARC was associated with
tumor cell capacity to migrate and invade, although its precise
role in tumor progression is still elusive. In the present study,
we show that SPARC produced by melanoma cells modulates
the antitumor activity of polymorphonuclear leukocytes
(PMN). Administration to nude mice of human melanoma
cells in which SPARC expression was transiently or stably
knocked down by antisense RNA (SPARC-sup cells) promoted
PMN recruitment and obliterated tumor growth even when
SPARC-sup cells accounted for only 10% of injected malignant
cells. In addition, SPARC-sup cells stimulated the in vitro
migration and triggered the antimelanoma cytotoxic capacity
of human PMN, an effect that was reverted in the presence of
SPARC purified from melanoma cells or by reexpressing
SPARC in SPARC-sup cells. Leukotrienes, interleukin 8, and
growth-related oncogene, in combination with Fas ligand and
interleukin 1, mediated SPARC effects. These data indicate
that SPARC plays an essential role in tumor evasion from
immune surveillance through the inhibition of the antitumor
PMN activity.