CD24 offers a therapeutic target for control of bladder cancer metastasis based on a requirement for lung colonization

Jonathan B. Overdevest, Shibu Thomas, Glen Kristiansen, Donna E. Hansel, Steven C. Smith, Dan Theodorescu

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

Metastasis is lethal in most bladder cancer patients. Expression of CD24, a glycosyl phosphatidylinositol (GPI)-linked sialoglycoprotein and cancer stem cell marker, is associated with metastatic progression in multiple cancer types, yet the role of CD24 in this process remains unclear. While developing a murine model of human metastatic bladder cancer, we observed that tumor cell CD24 expression correlated with a propensity to metastasize to the lung. Our immunohistochemical evaluation of 60 paired primary and metastatic human bladder cancer samples revealed increased intensity (P < 0.001) and frequency (P < 0.001) of CD24 expression in metastases. To directly evaluate the role of CD24 in metastatic colonization, we manipulated CD24 expression in human bladder cancer cell lines using short hairpin RNA depletion, cDNA overexpression, and fluorescenceactivated cell sorting selection. Although suppression of CD24 reduced acute tumor cell retention in the lungs of mice inoculated intravenously with cancer cells, this differential retention was no longer apparent after 24 hours, prompting us to evaluate the role of CD24 in lung colonization. Here, CD24 was found necessary for subsequent development of lung metastases. We next treated clinically detectable lung metastases in mice with anti-CD24 antibody and observed reduced tumor growth and prolonged survival. These findings suggest that CD24 is a lynchpin of metastatic progression and a promising therapeutic target for antimetastatic therapy.

Original languageEnglish (US)
Pages (from-to)3802-3811
Number of pages10
JournalCancer Research
Volume71
Issue number11
DOIs
StatePublished - Jun 1 2011
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'CD24 offers a therapeutic target for control of bladder cancer metastasis based on a requirement for lung colonization'. Together they form a unique fingerprint.

Cite this