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自发肿瘤荷瘤鼠模型中的天然卟啉。

Naturally-occurring porphyrins in a spontaneous-tumour bearing mouse model.

机构信息

IGM-CNR, Sezione Istochimica e Citometria, Dipartimento di Biologia Animale, Università di Pavia, 27100, Pavia, Italy.

出版信息

Photochem Photobiol Sci. 2011 Jul;10(7):1189-95. doi: 10.1039/c0pp00375a. Epub 2011 Apr 13.

DOI:10.1039/c0pp00375a
PMID:21487628
Abstract

An increase in naturally-occurring porphyrins has been described in the blood of subjects bearing different kinds of tumours, that has been proposed as an additional parameter for the diagnosis of occult cancer, although at present the reason for the phenomenon is not exactly defined. In this work the increase of porphyrins in plasma of tumour-bearing subjects has been investigated in parallel with their occurrence in other tissues, considering the systemic iron homeostasis subversion taking place in the presence of cancer. The transgenic female MMTV-neu mouse-developing spontaneous mammary adenocarcinoma has been used as an experimental model, in comparison to non-transgenic C1 mouse as a control. The spleen, accomplishing both hemocatheretic and hemopoietic functions in rodents, and the liver have been considered because of their deep engagement in heme metabolism, entailing both the fate of protoporphyrin IX (PpIX) as its ultimate precursor, and iron homeostasis. Investigations have been performed by means of microspectrofluorometric and image analysis of tissue autofluorescence (AF), and histochemical detection of non-heme iron. In tumour-bearing mouse, along with a marked PpIX presence in tumour, a PpIX enhancement in spleen and liver is observed, that is accompanied by a significant increase in plasma. The phenomenon can be related to a systemic alteration of heme metabolism induced by tumour cells to face their survival and proliferation requirements.

摘要

在患有不同类型肿瘤的受试者的血液中已经描述了天然卟啉的增加,这已被提议作为隐匿性癌症诊断的附加参数,尽管目前该现象的原因尚未明确界定。在这项工作中,考虑到癌症存在时发生的系统性铁平衡破坏,同时研究了荷瘤受试者血浆中卟啉的增加与其在其他组织中的发生情况。使用自发发生乳腺腺癌的转基因雌性 MMTV-neu 小鼠作为实验模型,与非转基因 C1 小鼠作为对照。脾,在啮齿动物中完成血液和造血功能,以及肝脏,由于它们深入参与血红素代谢,涉及原卟啉 IX(PpIX)作为其最终前体和铁平衡的命运,因此被考虑在内。通过组织自发荧光(AF)的微光谱荧光和图像分析以及非血红素铁的组织化学检测来进行研究。在荷瘤小鼠中,除了在肿瘤中观察到明显的 PpIX 存在外,还观察到脾和肝中的 PpIX 增强,这伴随着血浆中显著增加。该现象可与肿瘤细胞诱导的血红素代谢的系统性改变相关联,以满足其生存和增殖的需求。

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