Endoglin suppresses human prostate cancer metastasis

Minalini Lakshman, Xiaoke Huang, Vijayalakshmi Ananthanarayanan, Borko Jovanovic, Yueqin Liu, Clarissa S. Craft, Diana Romero, Calvin P.H. Vary, Raymond C. Bergan

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Endoglin is a transmembrane receptor that suppresses human prostate cancer (PCa) cell invasion. Small molecule therapeutics now being tested in humans can activate endoglin signaling. It is not known whether endoglin can regulate metastatic behavior, PCa tumor growth, nor what signaling pathways are linked to these processes. This study sought to investigate the effect of endoglin on these parameters. We used a murine orthotopic model of human PCa metastasis, designed by us to measure effects at early steps in the metastatic cascade, and implanted PCa cells stably engineered to express differing levels of endoglin. We now extend this model to measure cancer cells circulating in the blood. Progressive endoglin loss led to progressive increases in the number of circulating PCa cells as well as to the formation of soft tissue metastases. Endoglin was known to suppress invasion by activating the Smad1 transcription factor. We now show that it selectively activates specific Smad1-responsive genes, including JUNB, STAT1, and SOX4. Increased tumor growth and increased Ki67 expression in tissue was seen only with complete endoglin loss. By showing that endoglin increased TGFβ-mediated suppression of cell growth in vitro and TGFβ-mediated signaling in tumor tissue, loss of this growth-suppressive pathway appears to be implicated at least in part for the increased size of endoglin-deficient tumors. Endoglin is shown for the first time to suppress cell movement out of primary tumor as well as the formation of distant metastasis. It is also shown to co-regulate tumor growth and metastatic behavior in human PCa.

Original languageEnglish (US)
Pages (from-to)39-53
Number of pages15
JournalClinical and Experimental Metastasis
Volume28
Issue number1
DOIs
StatePublished - Jan 2011

Keywords

  • Circulating tumor cells
  • Endoglin
  • Metastasis
  • Prostate cancer
  • Transforming growth factor β

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Lakshman, M., Huang, X., Ananthanarayanan, V., Jovanovic, B., Liu, Y., Craft, C. S., Romero, D., Vary, C. P. H., & Bergan, R. C. (2011). Endoglin suppresses human prostate cancer metastasis. Clinical and Experimental Metastasis, 28(1), 39-53. https://doi.org/10.1007/s10585-010-9356-6