A novel interaction between perlecan protein core and progranulin. Potential effects on tumor growth

Eva M. Gonzalez, Maurizio Mongiat, Simon J. Slater, Raffaele Baffa, Renato V. Iozzo

Research output: Contribution to journalArticle

Abstract

In an in vivo search of novel partners for perlecan, a major heparan sulfate proteoglycan of basement membranes and cell surfaces, we identified progranulin, a secreted growth factor, as a strong interacting protein. Unambiguous interaction, first observed with the yeast two-hybrid system, was corroborated by co-immunoprecipitation studies using cell-free transcription/translation and transient cell transfection assays. The interaction of progranulin with perlecan domain V involved the first two laminin- and epidermal growth factor-like repeats. Within progranulin, the subdomains interacting most with perlecan harbored granulins F and B. Kinetics analysis of the interaction using surface plasmon resonance showed a saturable binding of relative low affinity (KD ∼1 μM). These results were supported by significant expression overlap of these two proteins in a series of ovarian tumor tissue microarrays. Progranulin was present within proliferating blood vessels of ovarian carcinomas and perivascular matrices, with a distribution similar to perlecan. Notably, both progranulin and domain V stimulated the growth of adrenal carcinoma cells. However, when used together in equimolar amounts, the two proteins counteracted each other's activity. Thus, progranulin/perlecan interaction could contribute to a fine regulation of tumor angiogenesis and could ultimately affect cancer growth.

Original languageEnglish
Pages (from-to)38113-38116
Number of pages4
JournalJournal of Biological Chemistry
Volume278
Issue number40
DOIs
Publication statusPublished - Oct 3 2003

ASJC Scopus subject areas

  • Biochemistry

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