Lung endothelial DPP IV promotes adhesion and metastasis of rat breast cancer cells via tumor cell surface-associated fibronectin

H. C. Cheng, M. Abdel-Ghany, R. C. Elble, B. U. Pauli

Research output: Contribution to journalArticlepeer-review

Abstract

Endothelial cells adhesion molecules are partly responsible for the distinct organ distribution of cancer metastases. Dipeptidyl peptidase IV (DPP IV) expressed by rat lung capillary endothelia is shown here to serve as an adhesion receptor for rat breast cancer cells and to promote lung colonization. In solid-state or rosetting adhesion assays, breast cancer cells bind to wtDPP IV and rDPP IV with high affinity. Adhesion is blocked by anti-DPP IV mAb 6A3 and competitively by soluble DPP IV. Similarly, the ability to colonize the lungs is impaired when tumor cells are incubated with soluble DPP IV prior to tail vein injection. The tumor cell ligand for DPP IV is cell surface-associated fibronectin (Fn), visualized as randomly dispersed stipples. These stipples represent polymeric Fn that can be precipitated by immobilized DPP IV from breast cancer cell lysates. The binding interaction between polymeric Fn and DPP IV is blocked by anti-Fn antiserum, but is unaffected by soluble plasma Fn (pFn) and, thus, can happen during hematogenous spread of cancer cells at high pFn concentrations. The presence of high affinity Fn-binding receptors (e.g., integrins) on many cancer cells, and the ability of these receptors to capture Fn molecules upon which self-association to high-molecular-weight polymers can occur, suggests that vascular arrest mediated by DPP IV/Fn-polymer binding might be a relatively common mechanism of metastasis to the lungs.

Original languageEnglish
Pages (from-to)A772
JournalFASEB Journal
Volume12
Issue number5
Publication statusPublished - 1998 Mar 20

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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