title: Role of CD44 in lymphokine-activated killer cell-mediated killing of melanoma.
abstract: In the current study, we examined the potential significance of CD44 expression on lymphokine-activated killer (LAK) cells in their interaction and killing of melanoma cells. Stimulation of splenocytes with IL-2 led to a significant increase in the expression of CD44 on T cells, NK cells, and NKT cells. Treatment of melanoma-bearing CD44 WT mice with IL-2 led to a significant reduction in the local tumor growth while treatment of melanoma-bearing CD44 KO mice with IL-2 was ineffective at controlling tumor growth. Furthermore, the ability of splenocytes from IL-2-treated CD44 KO mice to kill melanoma tumor targets was significantly reduced when compared to the anti-tumor activity of splenocytes from IL-2-treated CD44 WT mice. The importance of CD44 expression on the LAK cells was further confirmed by the observation that adoptively transferred CD44 WT LAK cells were significantly more effective than CD44 KO LAK cells at controlling tumor growth in vivo. Next, the significance of the increased expression of CD44 in tumor killing was examined and showed that following stimulation with IL-2, distinct populations of cells with low (CD44(lo)) or elevated (CD44(hi)) expression of CD44 are generated and that the CD44(hi) cells are responsible for killing of the melanoma cells. The reduced killing activity of the CD44 KO LAK cells did not result from reduced activation or expression of effector molecules but was due, at least in part, to a reduced ability to adhere to B16F10 tumor cells.
authors: Division of Basic Medical Sciences, Mercer University School of Medicine, 1550 College St, Macon, GA 31207, USA.
authors: Jingping
authors: J
authors: Sun
authors: Gabriela P
authors: GP
authors: Law
authors: Robert J
authors: RJ
authors: McKallip
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology*; D005434:Flow Cytometry; D015870:Gene Expression; D018960:Hyaluronan Receptors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D054992:Immunological Synapses / Q000187:drug effects / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology / Q000556:secondary; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics / Q000276:immunology
chemical_list: C476399:Cd44 protein, mouse; D016207:Cytokines; D018960:Hyaluronan Receptors; D007376:Interleukin-2