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Publication : Perforin is a major contributor to NK cell control of tumor metastasis.

First Author  Smyth MJ Year  1999
Journal  J Immunol Volume  162
Issue  11 Pages  6658-62
PubMed ID  10352283 Mgi Jnum  J:55335
Mgi Id  MGI:1337727 Doi  10.4049/jimmunol.162.11.6658
Citation  Smyth MJ, et al. (1999) Perforin is a major contributor to NK cell control of tumor metastasis. J Immunol 162(11):6658-62
abstractText  We provide the first demonstration, using experimental and spontaneous models of metastasis in C57BL/6 (B6) (RM-1 prostate carcinoma) and BALB/c (DA3 mammary carcinoma) mice, that tumor metastasis is primarily controlled by perforin-dependent cytotoxicity mediated by NK1.1+ cells. MHC class Ilow RM-1 and DA3 tumor cells were sensitive in vitro to Fas-mediated lysis or spleen NK cells in a perforin-dependent fashion. Perforin-deficient NK cells did not lyse these tumors, and perforin-deficient mice were 10-100-fold less proficient than wild-type mice in rejecting the metastasis of tumor cells to the lung. Fas ligand mutant gld mice displayed uncompromised protection against tumor metastasis. Depletion of NK subsets resulted in greater numbers of metastases than observed in perforin-deficient mice, suggesting that perforin-independent effector functions of NK cells may also contribute to protection from tumor metastasis.
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