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癌症衍生的 EMT 细胞在缺氧肿瘤微环境中 F-氟脱氧葡萄糖积累中的作用。

Involvement of cancer-derived EMT cells in the accumulation of F-fluorodeoxyglucose in the hypoxic cancer microenvironment.

机构信息

Laboratory of Animal Physiology, Graduate School of Environmental and Life Science, Okayama University, Okayama, Okayama, 700-8530, Japan.

Laboratory for Cellular Function Imaging, RIKEN Center for Biosystems Dynamics Research, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.

出版信息

Sci Rep. 2021 May 17;11(1):9668. doi: 10.1038/s41598-021-88414-1.

DOI:10.1038/s41598-021-88414-1
PMID:33994540
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8126561/
Abstract

A high rate of glycolysis, one of the most common features of cancer, is used in positron emission tomography (PET) imaging to visualize tumor tissues using F-fluorodeoxyglucose (F-FDG). Heterogeneous intratumoral distribution of F-FDG in tissues has been established in some types of cancer, and the maximum standardized uptake value (SUVmax) has been correlated with poor prognosis. However, the phenotype of cells that show high F-FDG accumulation in tumors remains unknown. Here, we combined quantitative micro-autoradiography with fluorescence immunohistochemistry to simultaneously visualize F-FDG distribution, the expression of multiple proteins, and hypoxic regions in the cancer microenvironment of a human A431 xenograft tumor in C.B-17/Icr-scid/scid mice. We found that the highest F-FDG accumulation was in cancer-derived cells undergoing epithelial-mesenchymal transition (EMT) in hypoxic regions, implicating these regions as a major contributor to increased glucose metabolism, as measured by F-FDG-PET.

摘要

糖酵解率高是癌症的最常见特征之一，正电子发射断层扫描（PET）成像利用 F-氟脱氧葡萄糖（F-FDG）对肿瘤组织进行可视化。在某些类型的癌症中，已经确定了组织中 F-FDG 的异质性分布，最大标准化摄取值（SUVmax）与预后不良相关。然而，表现出肿瘤中高 F-FDG 积累的细胞表型仍然未知。在这里，我们将定量微放射性自显影与荧光免疫组织化学相结合，同时可视化人 A431 异种移植肿瘤在 C.B-17/Icr-scid/scid 小鼠中的癌症微环境中的 F-FDG 分布、多种蛋白质的表达和缺氧区域。我们发现，在缺氧区域经历上皮-间充质转化（EMT）的癌源性细胞中积累了最高的 F-FDG，这表明这些区域是葡萄糖代谢增加的主要贡献者，正如 F-FDG-PET 所测量的那样。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f01/8126561/dca5b5050f19/41598_2021_88414_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f01/8126561/5a0edb0c862f/41598_2021_88414_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f01/8126561/c6af5110cd00/41598_2021_88414_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f01/8126561/c3a25df4fd7b/41598_2021_88414_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f01/8126561/b6b593d0b91d/41598_2021_88414_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f01/8126561/ef3a2f3a2d8e/41598_2021_88414_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f01/8126561/dca5b5050f19/41598_2021_88414_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f01/8126561/5a0edb0c862f/41598_2021_88414_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f01/8126561/c6af5110cd00/41598_2021_88414_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f01/8126561/c3a25df4fd7b/41598_2021_88414_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f01/8126561/b6b593d0b91d/41598_2021_88414_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f01/8126561/ef3a2f3a2d8e/41598_2021_88414_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f01/8126561/dca5b5050f19/41598_2021_88414_Fig6_HTML.jpg

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