The role of NK cells in selectin-dependent tumor suppression

Selectins are a small family of adhesion molecules that are critical for immune cell trafficking. In our laboratory, mice lacking all combinations of selectins have been generated. Previous work from our laboratory has demonstrated that, in the absence of selectins, human tumors transplanted subcutaneously into Rag2'- mice grow significantly larger. This implicates selectins and the innate immune system in tumor immune surveillance. We have extended the xenograft tumor model to immunocompetent C57BL/6 mice. Similarly to previous experiments, we found that many syngeneic tumors grow significantly larger in the triple selectin knockouts (ELP/) than in ELP+' control mice. The difference in tumor growth is most apparent in ELP'- and single L-selectin knockout (L-/) mice. P-selectin also contributes to selectin-dependent tumor suppression, while E-selectin does not appear to be involved. Since selectins are known to play a role in immune cell traffic, we explored recruitment defects in selectin knockout mice, and discovered that natural killer (NK) cell recruitment to tumors in Matrigel is impaired. NK cells in ELP-' and L'/ mice appear otherwise normal and functional. NK cells express L-selectin and selectin ligands, and are known to be tumoricidal. In mice depleted of NK cells, either pharmacologically by TM-P1 antibody injection, or genetically in NK-deficient GrzA-Ly49A transgenic mice, tumor growth is also significantly enhanced.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2008

Author dc:creator

• Sobolev, Olga, Ph. D. Massachusetts Institute of Technology

Advisor dc:contributor.advisor

• Richard O. Hynes.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/43227

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/43227