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Titolo:
REGULATION OF LOCAL HOST-MEDIATED ANTITUMOR MECHANISMS BY CYTOKINES -DIRECT AND INDIRECT EFFECTS ON LEUKOCYTE RECRUITMENT AND ANGIOGENESIS
Autore:
WATANABE M; MCCORMICK KL; VOLKER K; ORTALDO JR; WIGGINTON JM; BRUNDA MJ; WILTROUT RH; FOGLER WE;
Indirizzi:
NCI,FREDERICK CANC RES & DEV CTR,DIV BASIC SCI,EXPT IMMUNOL LAB,EXPT THERAPEUT SECT,BLDG 560 FREDERICK MD 21702 NCI,FREDERICK CANC RES & DEV CTR,DIV BASIC SCI,EXPT IMMUNOL LAB,EXPT THERAPEUT SECT FREDERICK MD 21702 NCI,FREDERICK CANC RES & DEV CTR,INTRAMURAL SUPPORT RES PROGRAM,SAIC FREDERICK FREDERICK MD 21702 HOFFMANN LA ROCHE INC,DEPT ONCOL NUTLEY NJ 07110
Titolo Testata:
The American journal of pathology
fascicolo: 5, volume: 150, anno: 1997,
pagine: 1869 - 1880
SICI:
0002-9440(1997)150:5<1869:ROLHAM>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
CELL-ADHESION MOLECULE-1; LEWIS-LUNG-CARCINOMA; IN-VIVO; ENDOTHELIAL CHANGES; CANCER METASTASIS; GROWTH-FACTOR; KILLER-CELLS; MICE; LYMPHOCYTES; INHIBITOR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
51
Recensione:
Indirizzi per estratti:
Citazione:
M. Watanabe et al., "REGULATION OF LOCAL HOST-MEDIATED ANTITUMOR MECHANISMS BY CYTOKINES -DIRECT AND INDIRECT EFFECTS ON LEUKOCYTE RECRUITMENT AND ANGIOGENESIS", The American journal of pathology, 150(5), 1997, pp. 1869-1880

Abstract

The regulation of tumor growth by cytokine-induced alterations in host effector cell recruitment and activation is intimately associated with leukocyte adhesion and angiogenic modulation. In the present study,we have developed a novel tumor model to investigate this complex series of events in response to cytokine administration. Gelatin sponges containing recombinant human basic fibroblast growth factor (rhFGFb) and B16F10 melanoma cells were implanted onto the serosal surface of the left lateral hepatic lobe in syngeneic C57BL/6 mice. The tumor modelwas characterized by progressive tumor growth initially localized within the sponge and the subsequent development of peritoneal carcinomatosis. Microscopic examination of the sponge matrix revealed well developed tumor-associated vascular structures and areas of endothelial cell activation as evidenced by leukocyte margination. Treatment of mice 3 days after sponge implantation with a therapeutic regimen consistingof pulse recombinant human interleukin-2 (rhIL-2) combined with recombinant murine interleukin-12 (rmIL-12) resulted in a marked hepatic mononuclear infiltrate and inhibition of tumor growth. In contrast to the control group, sponges from mice treated with rhIL-2/rmIL-12 demonstrated an overall lack of cellularity and vascular structure. The regimen of rhIL-2 in combination with rmIL-12 was equally effective againstgelatin sponge implants of rhFGFb/B16F10 melanoma in SCID mice treated with anti-asialo-GM1 in the absence of a mononuclear infiltration, suggesting that T, B, and/or NK cells were not the principal mediators of the anti-tumor response in this tumor model. The absence of vascularity within the sponge after treatment suggests that a potential mechanism of rhIL-2/rmIL-12 anti-tumor activity is the inhibition of neovascular growth associated with the establishment of tumor lesions. This potential mechanism could be dissociated from the known activities of these two cytokines to induce the recruitment and activation of host effector cells. Moreover, this model provides a unique opportunity to study the cellular and molecular mechanism(s) underlying both tumor angiogenesis and leukocyte recruitment to metastatic lesions.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/09/20 alle ore 07:28:00