Reactivity of tumor draining lymph nodes and the nitric oxide pathway

L.DAVEL,; ANA M EIJÁN; M.E.SALES,; A.ESPAÑOL,; A.DAGOSTINO,; I.PICCARDO,; L.LAURÍA,; E.SACERDOTE DE LUSTIG,; M.A.JASNIS

INTERNATIONAL JOURNAL OF ONCOLOGY

SPANDIDOS PUBL LTD

Lugar: Athenas; Año: 2002 vol. 20 p. 59 - 67

1019-6439

12. Int J Oncol. 2002 Jan;20(1):59-67. Reactivity of tumor-draining lymph nodes and the nitric oxide pathway. Davel L, Eijan AM, Sales ME, Español A, D´Agostino A, Piccardo I, Lauría L, De Lustig ES, Jasnis MA.Area de Investigacion, Instituto de Oncologia Angel H. Roffo, (1417) Buenos Aires, Argentina. davel@fmed.uba.ar 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 expressioncompared 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.