L-selectin can facilitate metastasis to lymph nodes in a transgenic mouse model of carcinogenesis.
L-selectin mediates homing of lymphocytes to lymph nodes (LN). Transgenic mice that express rat insulin promoter regulated simian virus 40 Tag (RIP-Tag) develop large, local cancers that metastasize to liver but not LN. To test whether this lack of LN metastases reflects their absence from the circulation, transgenic mice were produced that express Tag (T), L-selectin (L), and Escherichia coli LacZ (Z), in pancreatic beta cells. LTZ mice developed insulinomas that specifically had LN metastases; metastasis was blocked by an anti L-selectin mAb. LacZ(+) tumor cells from these LN homed to secondary LN upon transfer. These results suggest that the highly vascularized islet carcinomas are shedding tumor cells into the bloodstream, which is a necessary but insufficient condition for metastasis to occur; L-selectin can facilitate homing of such tumor cells to LN, resulting in metastasis.
Department of Pathology and Developmental Biology, Stanford School of Medicine, Stanford, CA 94305, USA.
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Qian
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Hanahan
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Weissman
D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D015197:Carcinogenicity Tests; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D019041:L-Selectin / Q000502:physiology*; D008207:Lymphatic Metastasis / Q000503:physiopathology*; D008208:Lymphatic System; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic
D000954:Antigens, Surface; C069886:L-selectin counter-receptors; D008565:Membrane Proteins; D019041:L-Selectin