Reactivity of tumor-draining lymph nodes and the nitric oxide pathway.
Regional lymph nodes are important in the generation of tumor-directed immune responses. The relationship between nitric oxide synthase (NOS) expression and the biological behavior of tumor-draining lymph node (TDLNs) cells in vivo was determined using a spontaneously arising BALB/c mammary adenocarcinoma S13. We first demonstrated a reduction of tumor size and tumor-induced angiogenesis by blocking NOS activity in vivo. TDLNs harvested from tumor-bearing mice (TBM) on day 16 after tumor implant, showed enhanced NOS activity and NOS expression compared to control nodes. Identification of the NOS isoforms present in TDLNs resulted in expression of neuronal NOS (nNOS), endothelial NOS (eNOS) and absence of inducible NOS (iNOS). TDLN cells admixed with tumor cells and inoculated into normal mice (Winn assay) induced a reduction of tumor growth although, when inoculated alone, were able to induce the formation of new blood vessels (angiogenesis). Our data indicate that the in vivo antitumor activity of TDLN cells is modulated by a balance between angiogenesis and antitumor effectors. In our model, when trafficking of leukocytes is obviated, the control of tumor growth by TDLN cells can be explained in part by an antitumor activity great enough to exceed the angiogenic component elicited by the same cells, leading to a reduction of tumor size.
Davel
Lilia
L
Area de Investigacion, Instituto de Oncologia Angel H. Roffo, (1417) Buenos Aires, Argentina. davel@fmed.uba.ar
Eijan
Ana M
AM
Sales
María E
ME
Español
Alejandro
A
D'Agostino
Agata
A
Piccardo
Inés
I
Lauría
Lilia
L
De Lustig
Eugenia S
ES
Jasnis
María A
MA
D000230:Adenocarcinoma / Q000098:blood supply / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015151:Immunoblotting; D008198:Lymph Nodes / Q000187:drug effects / Q000201:enzymology*; D008207:Lymphatic Metastasis; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009389:Neovascularization, Pathologic / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496321:Nos1 protein, mouse; C496317:Nos2 protein, mouse; C496315:Nos3 protein, mouse; D019331:NG-Nitroarginine Methyl Ester