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大鼠前列腺肿瘤可诱导远处器官的 DNA 合成。

Rat prostate tumors induce DNA synthesis in remote organs.

机构信息

Department of Medical Biosciences, Pathology, Umeå University, Building 6M, second floor, 901 87, Umeå, Sweden.

出版信息

Sci Rep. 2022 May 12;12(1):7908. doi: 10.1038/s41598-022-12131-6.

Abstract

Advanced cancers induce systemic responses. However, if such systemic changes occur already when aggressive tumors are small, have not been thoroughly characterized. Here, we examined how localized prostate cancers of different sizes and metastatic potential affected DNA synthesis in the rest of the prostate and in various remote organs. Non-metastatic Dunning R-3327 G (G) tumor cells, metastatic MatLyLu (MLL) tumor cells, or vehicle were injected into the prostate of immunocompetent rats. All animals received daily injections of Bromodeoxyuridine (BrdU), to label cells/daughter cells with active DNA synthesis. Equal sized G- and MLL-tumors, similarly increased BrdU-labeling in the prostate, lymph nodes and liver compared to tumor-free controls. Prior to metastasis, MLL-tumors also increased BrdU-labeling in bone marrow and lungs compared to animals with G-tumors or controls. In animals with MLL-tumors, BrdU-labeling in prostate, lungs, brown adipose tissue and skeletal muscles increased in a tumor-size-dependent way. Furthermore, MLL-tumors induced increased signs of DNA damage (γH2AX staining) and accumulation of CD68 + macrophages in the lungs. In conclusion, small localized prostate cancers increased DNA synthesis in several remote tissues in a tumor type- and size-dependent way. This may suggest the possibility for early diagnosis of aggressive prostate cancer by examining tumor-induced effects in other tissues.

摘要

晚期癌症会引起全身性反应。然而,如果在侵袭性肿瘤还很小时就已经发生了这种全身性变化,那么这些变化尚未被彻底描述。在这里,我们研究了不同大小和转移潜能的局部前列腺癌如何影响前列腺和各种远处器官的 DNA 合成。将非转移性 Dunning R-3327 G(G)肿瘤细胞、转移性 MatLyLu(MLL)肿瘤细胞或载体注射到免疫功能正常的大鼠前列腺中。所有动物均接受溴脱氧尿苷(BrdU)的每日注射,以标记具有活跃 DNA 合成的细胞/子细胞。与无肿瘤对照相比,同等大小的 G-和 MLL-肿瘤同样增加了前列腺、淋巴结和肝脏中的 BrdU 标记。在转移之前,与 G-肿瘤或对照相比,MLL-肿瘤还增加了骨髓和肺部中的 BrdU 标记。在患有 MLL-肿瘤的动物中,前列腺、肺部、棕色脂肪组织和骨骼肌中的 BrdU 标记以肿瘤大小依赖的方式增加。此外,MLL-肿瘤诱导肺部中 DNA 损伤(γH2AX 染色)的增加和 CD68+巨噬细胞的积累。总之,小的局部前列腺癌以肿瘤类型和大小依赖的方式增加了几个远处组织的 DNA 合成。这可能表明通过检查其他组织中的肿瘤诱导效应,早期诊断侵袭性前列腺癌的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa55/9098422/c35a5d52e691/41598_2022_12131_Fig1_HTML.jpg

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