This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Alvarez, M. J. Articles by Podhajcer, O. L. Search for Related Content PubMed PubMed Citation Articles by Alvarez, M. J. Articles by Podhajcer, O. L.

Secreted Protein Acidic and Rich in Cysteine Produced by Human Melanoma Cells Modulates Polymorphonuclear Leukocyte Recruitment and Antitumor Cytotoxic Capacity

¹ Leloir Institute, Consejo Nacional de Investigaciones Científicas y Técnicas, and ² José de San Martín Hospital, Faculty of Medicine, University of Buenos Aires; ³ Eva Perón Hospital, Buenos Aires, Argentina; and ⁴ Faculty of Veterinary Sciences, University of La Plata, La Plata, Argentina

Requests for reprints: Osvaldo L. Podhajcer, Fundación Instituto Leloir, Patricias Argentinas 435, C1405BWE Buenos Aires, Argentina. Phone: 54-11-4863-4015; Fax: 54-11-4865-2246; E-mail: opodhajcer{at}leloir.org.ar.

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.

This article has been cited by other articles:

				I. Podgorski, B. E. Linebaugh, J. E. Koblinski, D. L. Rudy, M. K. Herroon, M. B. Olive, and B. F. Sloane Bone Marrow-Derived Cathepsin K Cleaves SPARC in Bone Metastasis Am. J. Pathol., September 1, 2009; 175(3): 1255 - 1269. [Abstract] [Full Text] [PDF]

				M. De Cesare, C. Calcaterra, G. Pratesi, L. Gatti, F. Zunino, S. Menard, and A. Balsari Eradication of Ovarian Tumor Xenografts by Locoregional Administration of Targeted Immunotherapy Clin. Cancer Res., September 1, 2008; 14(17): 5512 - 5518. [Abstract] [Full Text] [PDF]

				K. A. Kelly, J. R. Allport, A. M. Yu, S. Sinh, E. H. Sage, R. E. Gerszten, and R. Weissleder SPARC is a VCAM-1 counter-ligand that mediates leukocyte transmigration J. Leukoc. Biol., March 1, 2007; 81(3): 748 - 756. [Abstract] [Full Text] [PDF]

				J. M. Challacombe, A. Suhrbier, P. G. Parsons, B. Jones, P. Hampson, D. Kavanagh, G. E. Rainger, M. Morris, J. M. Lord, T. T. T. Le, et al. Neutrophils Are a Key Component of the Antitumor Efficacy of Topical Chemotherapy with Ingenol-3-Angelate J. Immunol., December 1, 2006; 177(11): 8123 - 8132. [Abstract] [Full Text] [PDF]

				G. Robert, C. Gaggioli, O. Bailet, C. Chavey, P. Abbe, E. Aberdam, E. Sabatie, A. Cano, A. Garcia de Herreros, R. Ballotti, et al. SPARC Represses E-Cadherin and Induces Mesenchymal Transition during Melanoma Development. Cancer Res., August 1, 2006; 66(15): 7516 - 7523. [Abstract] [Full Text] [PDF]