Differential locomotion of long- and short-term IL-2-activated murine natural killer cells in a model matrix environment.
Tumour infiltration by activated natural killer (A-NK) cells is a pre-requisite for tumour eradication by adoptive NK cell transfer. Extravasated A-NK cells do not always succeed in reaching the crucial target cell conjugation. Therefore, we wished to study A-NK cell locomotion and interactions with melanoma cells in a matrix environment (Matrigel) by electron, confocal and fluorescence microscopy. Two distinct patterns of A-NK cell-mediated matrix disintegration were revealed during incubation of tumour cells and A-NK cells in Matrigel: (1) A-NK cells pre-cultured for 5 days altered the homogeneous texture of the Matrigel, an initial microporous appearance became a loose filamentous meshwork by 24 h. Matrix degrading protease inhibitors could not fully prevent this, but could delay the process; and (2) A-NK cells pre-cultured for 6 days or more, instead formed large excavations in the Matrigel leaving the remaining matrix less affected compared to the effects by the younger A-NK cells. By histochemical staining with Cupromeronic Blue, the excavations were shown to contain proteoglycan material. Protease inhibitors had no discernable effect on the development of the excavations. The conspicuous capacity of A-NK cells to disintegrate extracellular matrix and the formation of large excavations seems only partially to depend on matrix-degrading proteases. Formation of extracellular proteoglycan material is suggested to facilitate A-NK cell locomotion within a matrix environment.
Albertsson
P
P
Department of Oncology, Sahlgrenska University Hospital, Göteborg, Sweden. per.albertsson@oncology.gu.se
Basse
P H
PH
Edsparr
K
K
Kim
M H
MH
Goldfarb
R H
RH
Golfarb
R H
RH
Kitson
R P
RP
Lennernäs
B
B
Nannmark
U
U
Johansson
B R
BR
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology*; D018920:Coculture Techniques; D003094:Collagen; D004338:Drug Combinations; D006651:Histocytochemistry; D006801:Humans; D007211:Indoles / Q000737:chemistry; D007376:Interleukin-2 / Q000276:immunology*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007797:Laminin; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009942:Organometallic Compounds / Q000737:chemistry; D011509:Proteoglycans
D004338:Drug Combinations; D007211:Indoles; D007376:Interleukin-2; D007797:Laminin; D009942:Organometallic Compounds; D011509:Proteoglycans; C059485:matrigel; C015445:copper phthalocyanine; D003094:Collagen