AHNAK is highly expressed and plays a key role in cell migration and invasion in mesothelioma

Our plain-English summary of AHNAK is highly expressed and plays a key role in cell migration and invasion in mesothelioma, by H. Sudo, A.B. Tsuji, A. Sugyo, et al (International Journal of Oncology, 2014).

The study

• Authors: H. Sudo, A.B. Tsuji, A. Sugyo, M. Abe, O. Hino, T. Saga
• Journal: International Journal of Oncology
• Published: 2014;44(2):530-8
• Cited by: 38 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The worldwide incidence of the highly aggressive tumor mesothelioma is expected to increase. Mesothelioma is classified into three main histological subtypes: epithelioid, sarcomatoid and biphasic. Although the pathological diagnostic markers for epithelioid are established, to date no adequate marker for sarcomatoid mesothelioma has been found. Thus, a reliable diagnostic marker of sarcomatoid mesothelioma is necessary. In this study, to identify an unknown protein with 120 kDa expressed only in the mesothelioma cell line 211H, we conducted proteomic analysis and found five candidate proteins. One such protein, AHNAK, was highly expressed in all seven mesothelioma cell lines (211H, H28, H226, H2052, H2452, MESO1 and MESO4), but not in the mesothelial cell line MeT-5A by RT-PCR and immunofluorescence staining. Furthermore, we confirmed high AHNAK expression not only in xenografts but also in human mesothelioma specimens including sarcomatoid, epithelioid and biphasic mesothelioma using immunohistochemical staining. These findings suggest that AHNAK has the potential to be a new marker for detecting mesothelioma. Since AHNAK is involved in cell migration and invasion in other metastatic tumor cells, we conducted migration and invasion assays in mesothelioma cell lines. The number of migrating cells in six of seven mesothelioma cell lines and the number of invading cells in all seven cell lines were significantly increased compared with those in MeT-5A. Knockdown of AHNAK significantly reduced the cell migration and invasion ability in all seven mesothelioma cell lines. These results support further clinical evaluation of the association of AHNAK and metastasis in mesothelioma.

In plain English

This was a laboratory study by researchers in Japan of a protein called AHNAK in mesothelioma. It did not examine asbestos exposure. The authors identified AHNAK while analysing an unknown protein found in one mesothelioma cell line, 211H. AHNAK mRNA was significantly higher in all seven mesothelioma cell lines tested than in the mesothelial cell line MeT-5A, by 1.5- to 5.1-fold. Four of the cell lines grew as tumors in mice, and AHNAK was found in all four. In tumor tissue from 10 patients, AHNAK was detected in 9 of 10: 6 of 6 sarcomatoid, 2 of 2 epithelioid and 1 of 2 biphasic. The established marker ERC/mesothelin was found only in the 2 epithelioid samples. In lab-dish tests, six of seven mesothelioma cell lines migrated more than MeT-5A, and all seven invaded more. Reducing AHNAK significantly lowered migration and invasion in all seven lines. The authors concluded that AHNAK may have potential as a new marker for detecting mesothelioma, but that further clinical investigation is needed. They noted that a larger number of human specimens is required to confirm the findings.

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 study using mesothelioma cell lines, mouse xenograft tumors and resected human tumor specimens, including protein identification, staining and gene-knockdown experiments
• Who was studied: Seven human mesothelioma cell lines (211H, H28, H226, H2052, H2452, MESO1, MESO4) compared with the mesothelial cell line MeT-5A; xenograft tumors in nude mice; and tumor specimens from 10 patients (six sarcomatoid, two epithelioid, two biphasic) at Juntendo University Hospital, Japan. Dates are not given.
• Exposure: No asbestos or fiber exposure was studied. The study examined expression of the protein AHNAK and whether it is associated with cell migration and invasion.
• Main results:
  • Of five candidate proteins found only in 211H cells, AHNAK had the highest total score (1,186) and matched peptide number (24)
  • AHNAK mRNA in all seven mesothelioma cell lines was significantly higher (P<0.05) than in MeT-5A, by 1.5- to 5.1-fold
  • Four cell lines (211H, H226, MESO1, MESO4) formed tumors in mice, and AHNAK was expressed in all four xenograft tumors
  • In human specimens, AHNAK was detected in 90% (9/10): 6/6 sarcomatoid, 2/2 epithelioid, 1/2 biphasic
  • ERC/mesothelin was detected in 2/2 epithelioid specimens, 0/6 sarcomatoid and 0/2 biphasic
  • Migrating cells in six mesothelioma cell lines were 4.3- to 12.5-fold higher than in MeT-5A (P<0.01). There was no significant difference for H2052.
  • Invading cells in all seven mesothelioma cell lines were 33.5- to 143.9-fold higher than in MeT-5A (P<0.01)
  • AHNAK knockdown reduced migrating cells to less than 21% of negative control in six lines. In MESO1 the reduction was to 62%, still significant (P<0.01).
  • AHNAK knockdown significantly reduced invading cells in all seven cell lines compared with negative control siRNA
  • AHNAK expression level was not correlated with migration or invasion potency across the seven mesothelioma cell lines
• The authors' conclusion: The authors concluded that AHNAK has the potential to be a new marker for detecting mesothelioma, although further clinical investigation is needed. They also concluded that AHNAK could be involved in cell migration and invasion of mesothelioma cell lines.
• Limitations the authors state:
  • The findings need confirmation in a larger number of human specimens
  • The authors could not confirm by western blotting that the unknown 120 kDa protein was the AHNAK fragment, because no AHNAK antibody worked well for that method

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Histological Subtype, Epithelioid, Sarcomatoid, Biphasic Mesothelioma, Mesothelial Cells, Immunohistochemistry, Metastasis.

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