Involvement of the very late antigen 4 integrin on melanoma in interleukin 1-augmented experimental metastases

Angela Garofalo, Renato G S Chirivi, Chiara Foglieni, Rod Pigott, Roberta Mortarini, Ines Martin-Padura, Andrea Anichini, Andy J. Gearing, Francisco Sanchez-Madrid, Elisabetta Dejana, Raffaella Giavazzi

Research output: Contribution to journalArticlepeer-review

Abstract

We have previously reported that treatment with interleukin 1 (IL-1) induced the augmentation of lung tumor colonies by a human melanoma in nude mice. Here we have investigated the involvement of the α4β1 integrin, the very late antigen 4 (VLA-4) in this augmentation. A375M melanoma cells expressed high levels of VLA-4 and preferentially adhered to a surface coated with vascular cell adhesion molecule 1 (VCAM-1), the ligand for VLA-4 on activated endothelial cells. This adhesion was inhibited by treating tumor cells with saturating concentrations of mAb to VLA-4. The production of lung colonies was significantly enhanced in nude mice given an injection of IL-1 before A375M melanoma cells. Immunoperoxidase staining showed that VCAM-1 could be expressed on lung vascular endothelium of mice in response to IL-1. Pretreatment of melanoma cells with a mAb to VLA-4 completely abrogated the IL-1-induced augmentation of lung colonies. Using two metastatic melanoma clones (clones 2/4 and 2/60) that expressed different levels of VLA-4, we found that only VLA-4-bearing cells adhered to a VCAM-1-coated surface and formed enhanced numbers of lung colonies in IL-1-treated nude mice. This augmentation was inhibited by pretreating the tumor cells with anti-VLA-4 mAb. These results demonstrate, in vivo, the functional involvement of VLA-4 on melanoma cells in IL-1-mediated lung colony augmentation, most probably involving the interaction of tumor cells with VCAM-1 on activated endothelial cells.

Original languageEnglish
Pages (from-to)414-419
Number of pages6
JournalCancer Research
Volume55
Issue number2
Publication statusPublished - Jan 15 1995

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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