Journal of Molecular Medicine

, Volume 81, Issue 10, pp 600–612 | Cite as

Progranulin (granulin-epithelin precursor, PC-cell-derived growth factor, acrogranin) mediates tissue repair and tumorigenesis

  • Zhiheng He
  • Andrew BatemanEmail author
Invited review


Progranulin (Pgrn) is a pluripotent secreted growth factor that mediates cell cycle progression and cell motility. It activates the extracellular regulated kinases and phosphatidyl inositol-3 kinase signal cascades, among others, and increases expression of cyclins D and B. Structurally, it belongs to none of the well-established growth factor families. It regulates developmental events as diverse as the onset of cavitation in the preimplantation embryo and male-specific brain differentiation. During wound repair it promotes granulation and neovascularization. It regulates inflammation through a tripartite loop with secretory leukocyte protease inhibitor (SLPI) which protects pgrn from proteolysis, and elastase, which digests it to smaller peptides. Intact pgrn is anti-inflammatory through the inhibition of some of the actions of tumor necrosis factor, while the proteolytic peptides may stimulate the production of proinflammatory cytokines such as interleukin 8. Pgrn is highly expressed in aggressive cancer cell lines and clinical specimens including breast, ovarian, and renal cancers as well as gliomas. In experimental systems it confers an aggressive phenotype on poorly tumorigenic epithelial cancer cells. The malignancy of highly tumorigenic progranulin-expressing cell lines depends on the expression level of the pgrn gene since attenuating pgrn mRNA levels in pgrn-responsive cells greatly inhibits tumor progression. Given its actions in wound repair and tumorigenesis pgrn may prove a useful clinical target, both for prognosis and for therapy.


Growth factor Tumorigenesis Wound repair Neovascularization Inflammation 



Epidermal growth factor


Focal adhesion kinase


Fibroblast growth factor




Insulin-like growth factor


Mitogen-activated protein kinase


Mouse embryo fibroblast


Platelet-derived growth factor




Phosphatidylinositol-3 kinase


Secretory leukocyte protease inhibitor


Transforming growth factor-β


Epithelial transforming growth factor


Tumor necrosis factor


Vascular endothelial growth factor



A.B. acknowledges the Canadian Institutes for Health Research and the National Cancer Institute of Canada for financial support.


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© Springer-Verlag 2003

Authors and Affiliations

  1. 1.Vascular Cell Biology and Complications, Joslin Diabetes CenterHarvard Medical SchoolBostonUSA
  2. 2.Division of Experimental Medicine, McGill University, and Endocrine Research LaboratoryRoyal Victoria HospitalMontrealCanada

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