Potential protumor function of CD74 in clear cell renal cell carcinoma.

IF 3.4 3区生物学 Q3 CELL BIOLOGY Human Cell Pub Date : 2024-09-01 Epub Date: 2024-07-30 DOI:10.1007/s13577-024-01110-w

Ayano Ezaki, Hiromu Yano, Cheng Pan, Yukio Fujiwara, Toshiki Anami, Yuki Ibe, Takanobu Motoshima, Junji Yatsuda, Shigeyuki Esumi, Yuji Miura, Tomomi Kamba, Yoshihiro Komohara

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Abstract

CD74 is a transmembrane protein that functions as a specialized chaperone of HLA class II and CD74 in tumor cells was suggested to be involved in cell proliferation in several kinds of malignant tumors. CD74 is also known to be expressed in macrophages, therefore, we investigated the CD74 expression in clear cell renal cell carcinoma (ccRCC). Immunohistochemistry of CD74 indicated that CD74 was expressed not only in cancer cells but also macrophages. CD74 was detected in surface membrane and cytoplasm of cancer cells in 92 of 94 cases (98%) and of 87 of 94 cases (93%). CD74 was expressed both in cancer cells and TAMs in 86 of 94 cases (91%). In vitro studies using cancer cell lines and monocyte-derived macrophages stimulated by anti-CD74 antibodies showed that CD74 signal accelerated cancer cell proliferation and macrophage activation. However, macrophage activation via CD74 signal did not influence macrophage-mediated cancer cell growth. RNA-sequence of macrophages stimulated by anti-CD74 antibodies indicated that CD74 signal was associated to inflammatory responses in macrophages. In conclusion, we examined the expression and functional significance of CD74 in ccRCC using tissue specimens and cell culture studies. The function of CD74 was suggested to be different in cancer cells and in macrophages, and further studies are necessary to clarify the functional significance of CD74 in ccRCC.

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CD74在透明细胞肾细胞癌中的潜在原癌功能

CD74是一种跨膜蛋白，它是HLA II类的一种特殊伴侣蛋白，有人认为CD74在肿瘤细胞中的表达参与了多种恶性肿瘤的细胞增殖。CD74 在巨噬细胞中也有表达，因此我们研究了 CD74 在透明细胞肾细胞癌（ccRCC）中的表达。CD74 的免疫组化结果表明，CD74 不仅在癌细胞中表达，在巨噬细胞中也有表达。94例中有92例（98%）在癌细胞表面膜和细胞质中检测到CD74，94例中有87例（93%）在癌细胞表面膜和细胞质中检测到CD74。在 94 个病例中的 86 个（91%）中，CD74 在癌细胞和 TAMs 中均有表达。使用抗 CD74 抗体刺激癌细胞系和单核细胞衍生巨噬细胞进行的体外研究表明，CD74 信号可加速癌细胞增殖和巨噬细胞活化。然而，通过 CD74 信号激活巨噬细胞并不会影响巨噬细胞介导的癌细胞生长。抗 CD74 抗体刺激巨噬细胞的 RNA 序列表明，CD74 信号与巨噬细胞的炎症反应有关。总之，我们利用组织标本和细胞培养研究考察了 CD74 在 ccRCC 中的表达和功能意义。研究表明，CD74在癌细胞和巨噬细胞中的功能不同，因此有必要进一步研究CD74在ccRCC中的功能意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Human Cell CELL BIOLOGY-

CiteScore

5.90

自引率

2.30%

发文量

176

审稿时长

4.5 months

期刊介绍： Human Cell is the official English-language journal of the Japan Human Cell Society. The journal serves as a forum for international research on all aspects of the human cell, encompassing not only cell biology but also pathology, cytology, and oncology, including clinical oncology. Embryonic stem cells derived from animals, regenerative medicine using animal cells, and experimental animal models with implications for human diseases are covered as well. Submissions in any of the following categories will be considered: Research Articles, Cell Lines, Rapid Communications, Reviews, and Letters to the Editor. A brief clinical case report focusing on cellular responses to pathological insults in human studies may also be submitted as a Letter to the Editor in a concise and short format. Not only basic scientists but also gynecologists, oncologists, and other clinical scientists are welcome to submit work expressing new ideas or research using human cells.