Burgos Jonathan R, Iresjö Britt-Marie, Smedh Ulrika
Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden.
Oncol Rep. 2016 Apr;35(4):2425-30. doi: 10.3892/or.2016.4558. Epub 2016 Jan 14.
The aim of the present study was to explore central and peripheral host responses to an anorexia-cachexia producing tumor. We focused on neuroendocrine anorexigenic signals in the hypothalamus, brainstem, pituitary and from the tumor per se. Expression of mRNA for corticotropin-releasing hormone (CRH), cocaine- and amphetamine-regulated transcript (CART), nesfatin-1, thyrotropin (TSH) and the TSH receptor were explored. In addition, we examined changes in plasma TSH, CART peptides (CARTp) and serum amyloid P component (SAP). C57BL/6 mice were implanted with MCG101 tumors or sham-treated. A sham-implanted, pair‑fed (PF) group was included to delineate between primary tumor and secondary effects from reduced feeding. Food intake and body weight were measured daily. mRNA levels from microdissected mouse brain samples were assayed using qPCR, and plasma levels were determined using ELISA. MCG101 tumors expectedly induced anorexia and loss of body weight. Tumor-bearing (TB) mice exhibited an increase in nesfatin-1 mRNA as well as a decrease in CART mRNA in the paraventricular area (PVN). The CART mRNA response was secondary to reduced caloric intake whereas nesfatin-1 mRNA appeared to be tumor-specifically induced. In the pituitary, CART and TSH mRNA were upregulated in the TB and PF animals compared to the freely fed controls. Plasma levels for CARTp were significantly elevated in TB but not PF mice whereas levels of TSH were unaffected. The plasma CARTp response was correlated to the degree of inflammation represented by SAP. The increase in nesfatin-1 mRNA in the PVN highlights nesfatin-1 as a plausible candidate for causing tumor-induced anorexia. CART mRNA expression in the PVN is likely an adaptation to reduced caloric intake secondary to a cancer anorexia-cachexia syndrome (CACS)‑inducing tumor. The MCG101 tumor did not express CART mRNA, thus the elevation of plasma CARTp is host derived and likely driven by inflammation.
本研究的目的是探究宿主对产生厌食 - 恶病质的肿瘤的中枢和外周反应。我们聚焦于下丘脑、脑干、垂体以及肿瘤本身的神经内分泌厌食信号。研究了促肾上腺皮质激素释放激素（CRH）、可卡因和苯丙胺调节转录物（CART）、nesfatin - 1、促甲状腺激素（TSH）及其受体的mRNA表达。此外，我们检测了血浆TSH、CART肽（CARTp）和血清淀粉样蛋白P成分（SAP）的变化。将MCG101肿瘤植入C57BL/6小鼠体内或进行假处理。设置假植入、配对喂养（PF）组以区分原发性肿瘤和进食减少的继发效应。每天测量食物摄入量和体重。使用qPCR检测从小鼠脑微切割样本中提取的mRNA水平，并使用ELISA测定血浆水平。MCG101肿瘤如预期那样诱发了厌食和体重减轻。荷瘤（TB）小鼠室旁核（PVN）中nesfatin - 1 mRNA增加，而CART mRNA减少。CART mRNA的反应是热量摄入减少的继发结果，而nesfatin - 1 mRNA似乎是肿瘤特异性诱导的。在垂体中，与自由进食的对照组相比，TB组和PF组动物的CART和TSH mRNA上调。TB组小鼠血浆CARTp水平显著升高，而PF组小鼠未升高，但TSH水平未受影响。血浆CARTp反应与由SAP代表的炎症程度相关。PVN中nesfatin - 1 mRNA的增加突出了nesfatin - 1作为导致肿瘤诱导厌食的可能候选因素。PVN中CART mRNA的表达可能是对癌症厌食 - 恶病质综合征（CACS）诱导肿瘤继发的热量摄入减少的一种适应。MCG101肿瘤不表达CART mRNA，因此血浆CARTp的升高源自宿主，可能由炎症驱动。
