Suppressive roles of calreticulin in prostate cancer growth and metastasis

Mahesh Alur, Minh M. Nguyen, Scott E. Eggener, Feng Jiang, Soheil S. Dadras, Jeffrey Stern, Simon Kimm, Kim Roehl, James Kozlowski, Michael Pins, Marek Michalak, Rajiv Dhir, Zhou Wang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Calreticulin is an essential, multifunctional Ca2+-binding protein that participates in the regulation of intracellular Ca2+ homeostasis, cell adhesion, and chaperoning. Calreticulin is abundantly expressed and regulated by androgens in prostate epithelial cells. Given the importance of both calreticulin in multiple essential cellular activities and androgens in prostate cancer, we investigated the possibility of a role for calreticulin in prostate cancer progression. Immunohistochemistry revealed the down-regulation of calreticulin in a subset of human prostate cancer specimens. Prostate cancer cells overexpressing exogenous calreticulin produced fewer colonies in both monolayer culture and soft agar. Furthermore, calreticulin overexpression also inhibited tumor growth in the orthotopic PC3 xenograft tumor model and macroscopic lung metastasis in the rat Dunning AT3.1 prostate tumor model. To address the potential mechanism of calreticulin suppression of prostate cancer, we generated calreticulin mutants with different functional domains deleted. The calreticulin mutants containing the P-domain, which binds to other endoplasmic reticulum chaperone proteins, were sufficient for the suppression of PC3 growth in colony formation assays. Overall, our data support the hypothesis that calreticulin inhibits growth and/or metastasis of prostate cancer cells and that this suppression requires the P-domain.

Original languageEnglish (US)
Pages (from-to)882-890
Number of pages9
JournalAmerican Journal of Pathology
Volume175
Issue number2
DOIs
StatePublished - Aug 2009

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'Suppressive roles of calreticulin in prostate cancer growth and metastasis'. Together they form a unique fingerprint.

Cite this