[Systemic inflammation and experimental cancer in a murine model].
The link between cancer and inflammation in an organ or tissue has firmly been established on the basis that cancer tends to occur at sites of chronic inflammation and that local inflammatory processes can accelerate the growth of preexisting tumors in both animals and human beings. In contrast, the relationship between cancer and systemic inflammation has been less studied. In this work, we demonstrated that the growth of the murine fibrosarcoma MC-C, was accompanied by manifestations of systemic inflammation, as demonstrated by an increase in both the number of circulating polymorphonuclear neutrophils (PMN) and the serum concentration of the proinflammatory cytokines interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) and the acute phase proteins C reactive (CRP) and serum A amyloid (SAA). Two temporally separate peaks of systemic inflammation were detected during tumor development. The first was displayed during the first week after tumor inoculation. The second peak began around day 14 and its intensity was proportional to tumor size. In mice bearing a large MC-C tumor, a high number of circulating PMN and myeloid precursors were evident. Most of these cells exhibited activation evidenced by an increased reactive oxygen species generation and high expression of the Gr1+/Mac1+ markers. Inoculation of thioglycolate -which generates a transient systemic inflammation-accelerated the growth of MC-C tumor and reciprocally, inhibition of such systemic inflammation by using indomethacin, prevented that enhancing effect. This suggests that the systemic inflammation that the tumor generates on its own, could be part of its growth strategy.
División Medicina Experimental, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina.
Juan
J
Bruzzo
Paula
P
Chiarella
Gabriela
G
Fernández
Oscar D
OD
Bustuoabad
Raúl A
RA
Ruggiero
D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D016207:Cytokines / Q000097:blood*; D005354:Fibrosarcoma / Q000097:blood / Q000473:pathology*; D007249:Inflammation / Q000097:blood / Q000473:pathology*; D053583:Interleukin-1beta / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009374:Neoplasms, Experimental / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000032:analysis / Q000097:blood; D000685:Serum Amyloid A Protein / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D014408:Biomarkers, Tumor; D016207:Cytokines; D053583:Interleukin-1beta; D017382:Reactive Oxygen Species; D000685:Serum Amyloid A Protein; D014409:Tumor Necrosis Factor-alpha