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Stromal expression of SPARC in pancreatic adenocarcinoma

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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.

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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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  1. Department of Medical Oncology (INSERM U728–PRES Paris 7 Diderot), Beaujon University Hospital, Assistance Publique–Hôpitaux de Paris, 100 boulevard du Général Leclerc, 92110, Clichy-La-Garenne, France

    Cindy Neuzillet, Sandrine Faivre & Eric Raymond

  2. Department of Gastroenterology and Pancreatology, Beaujon University Hospital (AP-HP–PRES Paris 7 Diderot), 100 boulevard du Général Leclerc, 92110, Clichy-La-Garenne, France

    Cindy Neuzillet & Pascal Hammel

  3. AAREC Filia Research, 1 place Paul Verlaine, 92100, Boulogne-Billancourt, France

    Annemilaï Tijeras-Raballand

  4. Department of Pathology, Beaujon University Hospital (AP-HP–PRES Paris 7 Diderot), 100 boulevard du Général Leclerc, 92110, Clichy-La-Garenne, France

    Jérôme Cros

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Neuzillet, C., Tijeras-Raballand, A., Cros, J. et al. Stromal expression of SPARC in pancreatic adenocarcinoma. Cancer Metastasis Rev 32, 585–602 (2013). https://doi.org/10.1007/s10555-013-9439-3

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