Selective up-regulation of tumor necrosis factor receptor I in tumor-bearing rats with cancer-related cachexia.
Tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) are important mediators in cancer cachexia; however, the expression of these cytokines and their receptors in tumor-bearing animals is poorly characterized. We analyzed expression of TNF-alpha, IL-6, tumor necrosis factor (TNF-RI, TNF-RII) and interleukin 6 (IL-6R) receptors in the brain, kidney, spleen, liver, muscle, ascite tumors and serum, from Yoshida AH-130 hepatoma-bearing rats. TNF-alpha increased in the brain, spleen, liver, and muscle of cachectic animals; IL-6 increased in the liver and muscle. AH-130 cells expressed a good level of TNF-alpha; on the contrary, no TNF-alpha or IL-6 protein was detected in the serum of either tumor-bearing or control animals. TNF-RI mRNA was up-regulated in the spleen, liver and muscle of tumor-bearing rats. TNF-RI protein levels confirmed up-regulation in the spleen and liver, but failed to detect any increase in the muscle. Western blotting against TNF-RI revealed two bands of lower molecular weight in cachectic muscle, suggesting proteolysis involving TNF-RI. No significant increase of either TNF-RII or IL-6R was observed. This is the first demonstration of a selective up-regulation of TNF-RI in cancer cachexia and suggests that local production of TNF-alpha and IL-6 is a corner-stone in the induction/maintenance of this syndrome.
Catalano
Maria G
MG
Laboratorio di Endocrinologia Oncologica, Dipartimenti di Fisiopatologia Clinica and Oncologia, Università di Torino, I-10126 Turin, Italy.
Fortunati
Nicoletta
N
Arena
Katia
K
Costelli
Paola
P
Aragno
Manuela
M
Danni
Oliviero
O
Boccuzzi
Giuseppe
G
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D002100:Cachexia / Q000209:etiology / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D009374:Neoplasms, Experimental / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D051381:Rats; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
D015703:Antigens, CD; D015850:Interleukin-6; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D020395:Receptors, Interleukin-7; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha