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 journalArticle

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

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Integrin alpha4beta1
Interleukin-1
Integrins
Melanoma
Neoplasm Metastasis
Vascular Cell Adhesion Molecule-1
Lung
Nude Mice
Neoplasms
Endothelial Cells
Clone Cells
Vascular Endothelium
Cell Communication
Staining and Labeling
Ligands

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Involvement of the very late antigen 4 integrin on melanoma in interleukin 1-augmented experimental metastases. / Garofalo, Angela; Chirivi, Renato G S; Foglieni, Chiara; Pigott, Rod; Mortarini, Roberta; Martin-Padura, Ines; Anichini, Andrea; Gearing, Andy J.; Sanchez-Madrid, Francisco; Dejana, Elisabetta; Giavazzi, Raffaella.

In: Cancer Research, Vol. 55, No. 2, 15.01.1995, p. 414-419.

Research output: Contribution to journalArticle

Garofalo, A, Chirivi, RGS, Foglieni, C, Pigott, R, Mortarini, R, Martin-Padura, I, Anichini, A, Gearing, AJ, Sanchez-Madrid, F, Dejana, E & Giavazzi, R 1995, 'Involvement of the very late antigen 4 integrin on melanoma in interleukin 1-augmented experimental metastases', Cancer Research, vol. 55, no. 2, pp. 414-419.
Garofalo, Angela ; Chirivi, Renato G S ; Foglieni, Chiara ; Pigott, Rod ; Mortarini, Roberta ; Martin-Padura, Ines ; Anichini, Andrea ; Gearing, Andy J. ; Sanchez-Madrid, Francisco ; Dejana, Elisabetta ; Giavazzi, Raffaella. / Involvement of the very late antigen 4 integrin on melanoma in interleukin 1-augmented experimental metastases. In: Cancer Research. 1995 ; Vol. 55, No. 2. pp. 414-419.
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