Increased LFA-1-mediated homotypic cell adhesion is associated with the G1 growth arrest induced by rapamycin in a T cell lymphoma

Experimental Cell Research
F J DumontA Sirotina

Abstract

The immunosuppressive macrolide, rapamycin, impedes the G1 to S cell cycle progression in cytokine-stimulated normal lymphocytes and in certain autonomously proliferating cell lines. Here, we found that the rapamycin-induced growth arrest augments homotypic aggregation in the YAC-1 T cell lymphoma. The growth arrest and increased aggregation were both blocked by the rapamycin antagonist, L-685,818, which interacts with the intracellular binding proteins mediating rapamycin's biochemical action. Moreover, rapamycin-induced aggregation was not seen in YAC-1 cells mutants selected for resistance to the drug's antiproliferative effect. Although the inhibition of G1/S progression induced by serum deprivation also resulted in increased cellular aggregation, cell cycle blockade in late G1 by mimosine, early S phase by hydroxyurea, or G2/M by nocodazole all failed to do so. Furthermore, the aggregation induced by rapamycin was blocked by antibodies to the alpha (CD11a) or beta (CD18) subunits of the integrin, LFA-1, or to its ligands, ICAM-1 and ICAM-2, and did not occur in LFA-1-deficient YAC mutants. However, the surface expression of LFA-1, ICAM-1, or ICAM-2 was not augmented in cells aggregated by rapamycin. Finally, the serine/thr...Continue Reading

Citations

Mar 13, 2014·International Journal of Pharmaceutics·Robert F H WalterLutz Freitag
Mar 5, 2005·Blood·Manuela BattagliaMaria-Grazia Roncarolo
Jan 1, 1996·Life Sciences·F J Dumont, Q Su
May 25, 2021·Experimental Cell Research·Devi Prasad Vijayashankar, Tushar Vaidya

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.