The Journal of Experimental Medicine
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Published online 13 December 2005 doi:10.1084/jem.20051473
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 202, Number 12, 1679-1689
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ARTICLE

 Suppression of tumor formation in lymph nodes by L-selectin–mediated natural killer cell recruitment

Shihao Chen1, Hiroto Kawashima1, John B. Lowe2, Lewis L. Lanier3, and Minoru Fukuda1

1 Glycobiology Program, Cancer Research Center, The Burnham Institute for Medical Research, La Jolla, CA 92037
2 Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106
3 Department of Microbiology and Immunology and the Cancer Research Institute, University of California San Francisco, San Francisco, CA 94143

CORRESPONDENCE Minoru Fukuda: minoru{at}burnham.org

Natural killer (NK) cells are known to reject certain tumors in vivo; however, the ability of NK cells to prevent metastasis of tumors into secondary lymphoid organs has not been addressed. Here, we report that in tumor-bearing hosts, NK cells are recruited to regional lymph nodes in wild-type mice, but not in mice deficient for L-selectin or L-selectin ligands. By adoptive transfer and complete Freund's adjuvant stimulation experiments, we demonstrated that L-selectin on NK cells and L-selectin ligands on endothelial cells are essential for NK cell recruitment to lymph nodes. Furthermore, freshly isolated resident lymph node NK cells lysed tumors efficiently, and metastasis of B16 melanoma cells to draining lymph nodes was suppressed in wild-type or Rag-1–deficient mice, but not when NK cells were depleted. Although L-selectin–deficient NK cells efficiently lysed tumor cells in vitro, NK cell–dependent suppression of tumor metastasis was diminished in mice deficient for L-selectin or L-selectin ligands because of insufficient NK cell recruitment to lymph nodes. Moreover, tumor metastasis was substantially inhibited in L-selectin–deficient mice reconstituted with wild-type NK cells. These findings indicate that L-selectin–mediated NK cell recruitment plays a crucial role in the control of tumor metastasis into secondary lymphoid organs.

Abbreviations used: CFSE, carboxyfluorescein diacetate succinimidyl ester; MLN, mesenteric lymph node; PLN, peripheral lymph node; VLA, very late antigen.

L.L. Lanier and M. Fukuda contributed equally to this work.


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