Retinoic acid negatively regulates β4 integrin expression and suppresses the malignant phenotype in a Lewis lung carcinoma cell line

Carlo Gaetano, Antonella Melchiori, Adriana Albini, Robetto Benelli, Rita Falcioni, Andrea Modesti, A. Modica, Susanna Scarpa, Ada Sacchi

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Abstract

Retinoic acid (RA) is a potent inhibitor of the malignant phenotype and of tumour cell growth. We observed that in vitro RA treatment of a highly metastatic lung carcinoma cell line (C87) induced a marked reduction in the amount of the β4 integrin subunit. The downregulation of this adhesion molecule was assessed by immunofluorescence, immunoprecipitation, and northern analysis. In order to investigate the effects of RA on the malignant phenotype in C87 cells we performed morphological and functional analysis after RA treatment. We found that RA was able to produce marked changes in C87 cell shape, increasing the number of flat cells (90% of the total cell population), and significantly inhibiting the malignant and invasive phenotype of C87 cells. RA treatment suppressed their clonogenic potential in soft agar (control, 20±5; RA, 0), and strongly reduced their chemotactic and chemoinvasive capacity (chemotaxis: control, 231±5; RA, 28±0; chemoinvasion: control, 132±11; RA=2±1). FACS analysis and cell count, however, indicated that RA reduced the growth of C87 cells only partially. After 72 h of treatment we observed only a 10% reduction in the S phase fraction of the cell population. Finally, the reduced lung colony-forming ability, observed after i.v. injection of RA-treated cells (lung foci/animal: RA-treated cells, 1±0.1; untreated, 8.5±0.8), further supports the conclusion that in this murine lung carcinoma cell line a marked reduction in the expression of the β4 integrin subunit is associated with a marked inhibition of the malignant phenotype.

Original languageEnglish
Pages (from-to)63-72
Number of pages10
JournalClinical & Experimental Metastasis
Volume12
Issue number1
DOIs
Publication statusPublished - Jan 1994

Fingerprint

Lewis Lung Carcinoma
Tretinoin
Integrins
Phenotype
Cell Line
Lung
Cell Count
Carcinoma
Aptitude
Cell Shape
Chemotaxis
Therapeutics
Growth
S Phase
Immunoprecipitation
Population
Agar
Fluorescent Antibody Technique

Keywords

  • Integrins
  • invasion
  • metastasis

ASJC Scopus subject areas

  • Cancer Research

Cite this

Retinoic acid negatively regulates β4 integrin expression and suppresses the malignant phenotype in a Lewis lung carcinoma cell line. / Gaetano, Carlo; Melchiori, Antonella; Albini, Adriana; Benelli, Robetto; Falcioni, Rita; Modesti, Andrea; Modica, A.; Scarpa, Susanna; Sacchi, Ada.

In: Clinical & Experimental Metastasis, Vol. 12, No. 1, 01.1994, p. 63-72.

Research output: Contribution to journalArticle

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