Inhibition of growth and enhancement of differentiation of colorectal carcinoma cell lines by MAb MR6 and IL-4.
We have previously shown that expression of gp200-MR6, a molecule that is functionally associated with the interleukin-4 receptor (IL-4R), is lost from breast carcinoma cells as malignancy increases. Here we have analysed a series of colorectal carcinoma cell lines and show a similar decrease with increasing malignancy. Moreover, analysis of the HRA-19 cell line, which can exhibit a poorly or a well-differentiated phenotype according to culture conditions, shows that gp200-MR6 is weakly expressed on the former but strongly expressed on the latter. Functional analysis using either IL-4 or monoclonal antibody (MAb) MR6 and the well-differentiated cell line SW1222 revealed that MAb MR6 acts as an agonist for IL-4, with both reagents causing a dose-dependent inhibition of cell division, but greatly enhancing the glandular differentiation of SW1222 in three-dimensional collagen gels. These observations suggest that the gp200-MR6 molecule may act as the product of a tumour suppressor gene and that its loss may be a primary event in tumourigenesis.
Al-Tubuly
A A
AA
Department of Immunology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Spijker
R
R
Pignatelli
M
M
Kirkland
S C
SC
Ritter
M A
MA
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D015703:Antigens, CD; D000951:Antigens, Neoplasm / Q000276:immunology*; D002277:Carcinoma / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000473:pathology*; D003864:Depression, Chemical; D016147:Genes, Tumor Suppressor; D006023:Glycoproteins / Q000276:immunology* / Q000502:physiology; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000951:Antigens, Neoplasm; C093569:DEC-205 receptor; D006023:Glycoproteins; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D015847:Interleukin-4