Localization of CD26/DPPIV in nucleus and its nuclear translocation enhanced by anti-CD26 monoclonal antibody with anti-tumor effect

Our plain-English summary of Localization of CD26/DPPIV in nucleus and its nuclear translocation enhanced by anti-CD26 monoclonal antibody with anti-tumor effect, by K. Yamada, M. Hayashi, W. Du, et al (Cancer Cell International, 2009).

The study

• Authors: K. Yamada, M. Hayashi, W. Du, K. Ohnuma, M. Sakamoto, C. Morimoto, T. Yamada
• Journal: Cancer Cell International
• Published: 2009;9:17
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: CD26 is a type II, cell surface glycoprotein known as dipeptidyl peptidase (DPP) IV. Previous studies have revealed CD26 expression in T cell leukemia/lymphoma and malignant mesothelioma, and an inhibitory effect of anti-CD26 monoclonal antibody (mAb) against the growth of CD26+ cancer cells in vitro and in vivo. The function of CD26 in tumor development is unknown and the machinery with which the CD26 mAb induces its anti-tumor effect remains uncharacterized.

Results: The localization of CD26 in the nucleus of T cell leukemia/lymphoma cells and mesothelioma cells was shown by biochemical and immuno-electron microscopic analysis. The DPPIV enzyme activity was revealed in the nuclear fraction of T cell leukemia/lymphoma cells. These expressions of intra-nuclear CD26 were augmented by treatment with the CD26 mAb, 1F7, with anti-tumor effect against the CD26+ T cell leukemia/lymphoma cells. In contrast, the CD26 mAb, 5F8, without anti-tumor effect, did not augment CD26 expressions in the nucleus. Biotin-labeled, cell surface CD26 translocated into the nucleus constantly, and this translocation was enhanced with 1F7 treatment but not with 5F8.

Conclusion: These results indicate that the intra-nuclear CD26 which moves from plasma membrane may play certain roles in cell growth of human cancer cells.

In plain English

This was a laboratory study of cultured human cancer cells, not of people, and it did not look at asbestos exposure. The authors studied CD26, a protein found on some cancer cells. They used a mesothelioma cell line (JMN), a T-cell lymphoma line (Karpas 299), and Jurkat cells with or without added CD26, and separated the cells into membrane, cytoplasm and nucleus portions. CD26 was found in the nucleus as well as elsewhere in the cell, and the mesothelioma line had relatively more CD26 in the nucleus than the T-cell lines. CD26 enzyme activity was found in the nucleus portions of the CD26-carrying Jurkat cells and the Karpas 299 cells. Earlier studies reported that antibody 1F7 inhibits T-cell growth. In this study, 1F7 raised nuclear CD26 within one hour and lowered membrane CD26, while antibody 5F8 did not. Surface CD26 moved into the nucleus constantly, and more so after 1F7, but this effect was slight in the mesothelioma cells. The authors concluded that nuclear CD26 may play a role in cancer cell growth or survival. They stated that how it reaches the nucleus remains unknown.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory experiment on cultured human cancer cell lines (biochemical fractionation, immunoblotting, immuno-electron microscopy, enzyme assays, cell-surface labeling)
• Who was studied: Human cell lines: Karpas 299 (anaplastic large T-cell lymphoma), JMN (mesothelioma), Jurkat cells (J/Wt, CD26-negative) and Jurkat cells containing a CD26 expression vector (J/CD26)
• Exposure: No asbestos exposure was studied. Cells were treated with the anti-CD26 monoclonal antibodies 1F7 or 5F8, or with control mouse IgG1. Earlier studies cited by the authors reported that 1F7 inhibits T-cell growth and that 5F8 has no such effect.
• Main results:
  • CD26 was detected in the nuclear fraction of the cells, as well as in the membrane and cytoplasmic fractions.
  • The JMN mesothelioma cell line showed relatively higher CD26 levels in the nuclear fraction than the two T-cell lines.
  • By electron microscopy, CD26 was spread diffusely through the nucleus of Karpas 299 cells. In JMN mesothelioma cells it was clustered in dense areas such as the chromatin structure.
  • DPPIV enzyme activity was detected in the nuclear and cytosolic fractions of J/CD26 and Karpas 299 cells, and it was inhibited by diprotin A.
  • In J/CD26 cells, nuclear CD26 peaked within one hour of treatment with 1F7, but not with 5F8 or control IgG1. Membrane CD26 decreased within one hour of 1F7 treatment.
  • Labeled cell-surface CD26 was always present in the nucleus of J/CD26 cells, including with control IgG1, indicating constant movement into the nucleus.
  • Labeled surface CD26 increased in the nuclear fraction of Karpas 299 cells after 1F7 treatment, compared with IgG1.
  • In the JMN mesothelioma cells, the effects of 1F7 on movement of CD26 into the nucleus were slight.
• The authors' conclusion: The authors concluded that CD26 inside the nucleus may play a role in the proliferation or survival of cancer cells.
• Limitations the authors state:
  • The authors state that the mechanism by which CD26 moves into the nucleus, and how 1F7 enhances this movement, remains unknown.

Topics

Medical terms in this study, explained in our Lexicon: Translocation, Monoclonal Antibody, Glycoprotein, Mesothelioma.

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