A naturally occurring truncated β3 integrin in tumor cells: Native anti-integrin involved in tumor cell motility

Rongxian Jin, Mohit Trikha, Yinlong Cai, David Grignon, Kenneth V. Honn

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Alternatively spliced integrins may play an important role in integrin mediated tumor cell adhesion, spreading, and migration. Here we report in human tumor cells a naturally occurring alternatively spliced variant of the β3 integrin [i.e., truncated (tr) β3] that lacked a cytoplasmic and a transmembrane domain. The presence of trβ3 was demonstrated at the mRNA level by RT-PCR, cloning, and sequencing; at the protein level by immunohistochemistry and Western Blotting. The alternately spliced β3 integrin was detected in human prostate carcinomas, breast carcinomas, and melanoma cells. Expression in vivo was confirmed by immunohistochemistry with an antibody to trβ3 that does not recognize wild type β3. Tumor cells secreted this protein and deposited it on the extracellular matrix. Secreted trβ3 inhibited adhesion of melanoma and prostate cancer cells to fibronectin and vitronectin, which was partially reversed by adsorption of trβ3 from the media. Confocal microscopy and time lapse live cell microscopy demonstrated that trβ3 distributed to the trailing edge of migrating cells, which may represent an alternative cell detachment mechanism in these cells. Results suggest that trβ3 may act as an anti-integrin and play a crucial role in cell migration, which is an important process in tumor invasion and metastasis.

Original languageEnglish (US)
Pages (from-to)1559-1568
Number of pages10
JournalCancer Biology and Therapy
Volume6
Issue number10
DOIs
StatePublished - Oct 2007

Keywords

  • Alternative splicing
  • Anti-integrin
  • Integrin β3
  • Metastasis
  • Motility
  • Secretion
  • Tumor

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

Fingerprint Dive into the research topics of 'A naturally occurring truncated β3 integrin in tumor cells: Native anti-integrin involved in tumor cell motility'. Together they form a unique fingerprint.

  • Cite this