Related Experiment Videos
Expression and ligand-binding function of the integrin alpha 4 beta 1 (VLA-4) on neural-crest-derived tumor cell
1Department of Immunology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Abstract:
Human neural-crest-derived tumor cell lines, including three neuroblastomas, an astrocytoma, a glioblastoma, a rhabdomyosarcoma and a melanoma were screened for the expression of the integrin alpha 4 beta 1 (VLA-4). The neuroblastomas IMR-32 and SK-N-SH, the astrocytoma 131-INI, the glioblastoma Fogerty and the rhabdomyosarcoma TE-671 expressed alpha 4 beta 1 as determined by cytofluorometry and immunoprecipitation. Another neuroblastoma line, LA-N-1, did not express alpha 4 beta 1. Analysis of immunoprecipitated alpha 4 beta 1 showed that the alpha 4 subunit from the various cell types differed in relative molecular weight (M(r)). The variability in the observed M(r) could be accounted for by differences in the levels of N-linked glycosylation. The observed variability in M(r) did not appear to affect function since intact cells and solubilized alpha 4 beta 1 bound to a synthetic peptide identical in sequence to the CS-1 region of the alternatively spliced IIICS domain of fibronectin, a known alpha 4 beta 1 ligand.
Insights
Integrin alpha 4 beta 1 (VLA-4) is expressed in most human neural-crest-derived tumor cells, with variations in its molecular weight due to glycosylation. This integrin maintains its fibronectin-binding function despite these variations.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Integrin alpha 4 beta 1 (VLA-4) plays a role in cell adhesion and migration.
- Neural-crest-derived tumors represent a diverse group of cancers.
Purpose of the Study:
- To investigate the expression of VLA-4 in various human neural-crest-derived tumor cell lines.
- To analyze the characteristics and function of VLA-4 in these cells.
Main Methods:
- Screening of tumor cell lines for VLA-4 expression using cytofluorometry and immunoprecipitation.
- Analysis of the alpha 4 subunit's molecular weight and glycosylation.
- Assessment of VLA-4 binding to a synthetic fibronectin peptide.
Main Results:
- VLA-4 was expressed in neuroblastomas, astrocytoma, glioblastoma, and rhabdomyosarcoma cell lines, but not in one neuroblastoma line (LA-N-1).
- The alpha 4 subunit exhibited variable molecular weights across different cell types, attributed to N-linked glycosylation differences.
- Despite molecular weight variations, VLA-4 retained its ability to bind to fibronectin.
Conclusions:
- VLA-4 is commonly expressed in human neural-crest-derived tumors.
- Glycosylation patterns of the alpha 4 subunit can vary, influencing its molecular weight.
- Functional VLA-4-fibronectin interactions are preserved despite observed glycosylation-dependent molecular weight heterogeneity.