Macrophage-derived SPARC bridges tumor cell-extracellular matrix interactions toward metastasis

Sabina Sangaletti, Emma Di Carlo, Silvia Gariboldi, Silvia Miotti, Barbara Cappetti, Mariella Parenza, Cristiano Rumio, Rolf A. Brekken, Claudia Chiodoni, Mario P. Colombo

Research output: Contribution to journalArticle

107 Scopus citations

Abstract

Other than genetic imprinting and epithelial to mesenchymal transition, cancer cells need interaction with the nearby stroma toward metastasis. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein known to regulate extracellular matrix (ECM) deposition and cell-ECM interaction. Gene expression profiles associate SPARC to malignant progression. Using reciprocal bone marrow chimeras between SPARC knockout and wild-type mice, we show that SPARC produced by inflammatory cells is necessary for spontaneous, but not experimental, i.v. metastasis. Macrophage-derived SPARC induces cancer cell migration and enhances their migration to other ECM proteins at least through αvβ5 integrin. Indeed, RNA interference knockdown of β5 integrin expression reduces cell migration in vitro and metastasis in vivo. Together these results show that macrophage-derived SPARC takes part in metastasis, acting at the step of integrin-mediated migration of invasive cells.

Original languageEnglish (US)
Pages (from-to)9050-9059
Number of pages10
JournalCancer research
Volume68
Issue number21
DOIs
StatePublished - Nov 1 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Sangaletti, S., Di Carlo, E., Gariboldi, S., Miotti, S., Cappetti, B., Parenza, M., Rumio, C., Brekken, R. A., Chiodoni, C., & Colombo, M. P. (2008). Macrophage-derived SPARC bridges tumor cell-extracellular matrix interactions toward metastasis. Cancer research, 68(21), 9050-9059. https://doi.org/10.1158/0008-5472.CAN-08-1327