Cancer and Metastasis Reviews

, Volume 32, Issue 3–4, pp 585–602 | Cite as

Stromal expression of SPARC in pancreatic adenocarcinoma

  • Cindy Neuzillet
  • Annemilaï Tijeras-Raballand
  • Jérôme Cros
  • Sandrine Faivre
  • Pascal Hammel
  • Eric Raymond
NON-THEMATIC REVIEW

Abstract

Pancreatic ductal adenocarcinoma (PDAC) stands as the poorest prognostic tumor of the digestive tract, with a 5-year survival rate of less than 5 %. Therapeutic options for unresectable PDAC are extremely limited and there is a pressing need for expanded therapeutic approaches to improve current options available with gemcitabine-based regimens. With PDAC displaying one of the most prominent desmoplastic stromal reactions of all carcinomas, recent research has focused on the microenvironment surrounding PDAC cells. Secreted protein acid and rich in cysteine (SPARC), which is overexpressed in PDAC, may display tumor suppressor functions in several cancers (e.g., in colorectal, ovarian, prostate cancers, and acute myelogenous leukemia) but also appears to be overexpressed in other tumor types (e.g., breast cancer, melanoma, and glioblastoma). The apparent contradictory functions of SPARC may yield inhibition of angiogenesis via inhibition of vascular endothelial growth factor, while promoting epithelial-to-mesenchymal transition and invasion through matrix metalloprotease expression. This feature is of particular interest in PDAC where SPARC overexpression in the stroma stands along with inhibition of angiogenesis and promotion of cancer cell invasion and metastasis. Several therapeutic strategies to deplete stromal tissue have been developed. In this review, we focused on key preclinical and clinical data describing the role of SPARC in PDAC biology, the properties, and mechanisms of delivery of drugs that interact with SPARC and discuss the proof-of-concept clinical trials using nab-paclitaxel.

Keywords

Pancreatic cancer Pancreatic adenocarcinoma SPARC Extracellular matrix Nab-paclitaxel EMT 

Notes

Acknowledgments

This work was supported by the Foundation Nelia & Amadeo Barleta and by the Association pour l’Aide à la Recherche & l’Enseignement en Cancérologie. The authors thank Sarah MacKenzie for manuscript editing. The authors also sincerely thank Prof. Philippe Ruszniewski, Dr. Maria Eugenia Riveiro, Dr. Maria Serova, and Dr. Armand de Gramont for thorough review and wise criticisms of the manuscript, which have strongly contributed to the quality of this review.

Conflict of interest

Pascal Hammel is a consultant for Novartis, Pfizer, and Ipsen; Sandrine Faivre is a consultant for Merck, Pfizer, Novartis, Bayer, and Lilly; and Eric Raymond is a consultant for Pfizer, Novartis, Bayer, and Lilly. Other authors have no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Cindy Neuzillet
    • 1
    • 2
  • Annemilaï Tijeras-Raballand
    • 3
  • Jérôme Cros
    • 4
  • Sandrine Faivre
    • 1
  • Pascal Hammel
    • 2
  • Eric Raymond
    • 1
  1. 1.Department of Medical Oncology (INSERM U728–PRES Paris 7 Diderot)Beaujon University Hospital, Assistance Publique–Hôpitaux de ParisClichy-La-GarenneFrance
  2. 2.Department of Gastroenterology and PancreatologyBeaujon University Hospital (AP-HP–PRES Paris 7 Diderot)Clichy-La-GarenneFrance
  3. 3.AAREC Filia ResearchBoulogne-BillancourtFrance
  4. 4.Department of PathologyBeaujon University Hospital (AP-HP–PRES Paris 7 Diderot)Clichy-La-GarenneFrance

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